{"id":2527,"date":"2016-06-02T17:11:43","date_gmt":"2016-06-02T17:11:43","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/biologyxwaymakerxmaster\/?post_type=chapter&#038;p=2527"},"modified":"2023-09-05T22:07:27","modified_gmt":"2023-09-05T22:07:27","slug":"dna-replication","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/chapter\/dna-replication\/","title":{"raw":"DNA Replication","rendered":"DNA Replication"},"content":{"raw":"<h2>What you'll learn to do: Explain the role of complementary base pairing in the precise replication process of DNA<\/h2>\r\nIn this outcome, we'll learn more about the precise structure of DNA and how it replicates. Watch this video for a quick introduction to this topic:\r\n\r\nhttps:\/\/youtu.be\/TNKWgcFPHqw\r\n<div class=\"textbox learning-objectives\">\r\n<h3>Learning Outcomes<\/h3>\r\n<ul>\r\n \t<li>Outline the basic steps in DNA replication<\/li>\r\n \t<li>Identify the major enzymes that play a role in DNA replication<\/li>\r\n \t<li>Identify the key proofreading processes in DNA replication<\/li>\r\n<\/ul>\r\n<\/div>\r\n<h2>Basics of DNA Replication<\/h2>\r\n[caption id=\"attachment_4411\" align=\"alignright\" width=\"400\"]<img class=\" wp-image-4411\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/02\/02000938\/Figure_14_03_01a.jpg\" alt=\"Illustration shows the conservative, semi-conservative, and dispersive models of DNA synthesis. In the conservative model, when DNA is replicated and both newly synthesized strands are paired together. In the semi-conservative model, each newly synthesized strand pairs with a parent strand. In the dispersive model, newly synthesized DNA is interspersed with parent DNA within both DNA strands.\" width=\"400\" height=\"404\" \/> Figure\u00a01. The three suggested models of DNA replication. Grey indicates the original DNA strands, and blue indicates newly synthesized DNA.[\/caption]\r\n\r\nThe elucidation of the structure of the double helix provided a hint as to how DNA divides and makes copies of itself. This model suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. What was not clear was how the replication took place. There were three models suggested: conservative, semi-conservative, and dispersive (see Figure\u00a01).\r\n\r\nIn <strong>conservative replication<\/strong>, the parental DNA remains together, and the newly formed daughter strands are together. The <strong>semi-conservative<\/strong> method suggests that each of the two parental DNA strands act as a template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or \u201cold\u201d strand and one \u201cnew\u201d strand. In the <strong>dispersive model<\/strong>, both copies of DNA have double-stranded segments of parental DNA and newly synthesized DNA interspersed.\r\n\r\nMeselson and Stahl were interested in understanding how DNA replicates. They grew\u00a0<em>E. coli<\/em> for several generations in a medium containing a \u201cheavy\u201d isotope of nitrogen (<sup>15<\/sup>N) that gets incorporated into nitrogenous bases, and eventually into the DNA (Figure\u00a02).\r\n\r\n[caption id=\"attachment_1430\" align=\"aligncenter\" width=\"800\"]<img class=\"size-full wp-image-1430\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/05\/02184216\/Figure_14_03_02.jpg\" alt=\"Illustration shows an experiment in which E. coli was grown initially in media containing ^{15}N nucleotides. When the DNA was extracted and run in an ultracentrifuge, a band of DNA appeared low in the tube. The culture was next placed in ^{14}N medium. After one generation, all of the DNA appeared in the middle of the tube, indicating that the DNA was a mixture of half ^{14}N and half ^{15}N DNA. After two generations, half of the DNA appeared in the middle of the tube, and half appeared higher up, indicating that half the DNA contained 50% ^{15}N, and half contained ^{14}N only. In subsequent generations, more and more of the DNA appeared in the upper, ^{14}N band.\" width=\"800\" height=\"698\" \/> Figure\u00a02. Meselson and Stahl experimented with E. coli grown first in heavy nitrogen (<sup>15<\/sup>N) then in <sup>14<\/sup>N. DNA grown in <sup>15<\/sup>N (red band) is heavier than DNA grown in <sup>14<\/sup>N (orange band), and sediments to a lower level in cesium chloride solution in an ultracentrifuge. When DNA grown in <sup>15<\/sup>N is switched to media containing <sup>14<\/sup>N, after one round of cell division the DNA sediments halfway between the <sup>15<\/sup>N and <sup>14<\/sup>N levels, indicating that it now contains fifty percent <sup>14<\/sup>N. In subsequent cell divisions, an increasing amount of DNA contains <sup>14<\/sup>N only. This data supports the semi-conservative replication model. (credit: modification of work by Mariana Ruiz Villareal)[\/caption]\r\n\r\nThe\u00a0<em>E. coli<\/em> culture was then shifted into medium containing <sup>14<\/sup>N and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was centrifuged at high speeds in an ultracentrifuge. Some cells were allowed to grow for one more life cycle in <sup>14<\/sup>N and spun again. During the density gradient centrifugation, the DNA is loaded into a gradient (typically a salt such as cesium chloride or sucrose) and spun at high speeds of 50,000 to 60,000 rpm. Under these circumstances, the DNA will form a band according to its density in the gradient. DNA grown in <sup>15<\/sup>N will band at a higher density position than that grown in <sup>14<\/sup>N. Meselson and Stahl noted that after one generation of growth in <sup>14<\/sup>N after they had been shifted from <sup>15<\/sup>N, the single band observed was intermediate in position in between DNA of cells grown exclusively in <sup>15<\/sup>N and <sup>14<\/sup>N. This suggested either a semi-conservative or dispersive mode of replication. The DNA harvested from cells grown for two generations in <sup>14<\/sup>N formed two bands: one DNA band was at the intermediate position between <sup>15<\/sup>N and <sup>14<\/sup>N, and the other corresponded to the band of <sup>14<\/sup>N DNA. These results could only be explained if DNA replicates in a semi-conservative manner. Therefore, the other two modes were ruled out.\r\n\r\nDuring DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or \u201cold\u201d strand. When two daughter DNA copies are formed, they have the same sequence and are divided equally into the two daughter cells.\r\n<div class=\"textbox learning-objectives\">\r\n<h3>In Summary: Basics of DNA Replication<\/h3>\r\nThe model for DNA replication suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. In conservative replication, the parental DNA is conserved, and the daughter DNA is newly synthesized. The semi-conservative method suggests that each of the two parental DNA strands acts as template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or \u201cold\u201d strand and one \u201cnew\u201d strand. The dispersive mode suggested that the two copies of the DNA would have segments of parental DNA and newly synthesized DNA. Experimental evidence showed DNA replication is semi-conservative.\r\n\r\n<\/div>\r\n<h2>Major Enzymes<\/h2>\r\nThe process of <strong>DNA replication<\/strong> is catalyzed by a type of enzyme called <strong>DNA polymerase<\/strong> (<em class=\"italic\">poly<\/em> meaning many, <em class=\"italic\">mer<\/em> meaning pieces, and -<em class=\"italic\">ase<\/em> meaning enzyme; so an enzyme that attaches many pieces of DNA). Observe Figure 3: the double helix of the original DNA molecule separates (blue) and new strands are made to match the separated strands. The result will be two DNA molecules, each containing an old and a new strand. Therefore, DNA replication is called semiconservative. The term <em class=\"bold\">semiconservative<\/em> refers to the fact that half of the original molecule (one of the two strands in the double helix) is \u201cconserved\u201d in the new molecule. The original strand is referred to as the <em class=\"bold\">template strand<\/em> because it provides the information, or template, for the newly synthesized strand.\r\n\r\n[caption id=\"attachment_2570\" align=\"aligncenter\" width=\"1024\"]<img class=\"wp-image-2570 size-large\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172248\/DNA_replication_split_horizontal.svg_-1024x508.png\" alt=\"Stylized 3' synthesis shown, no enzymes in diagram.\" width=\"1024\" height=\"508\" \/> Figure\u00a03. By Madprime(wikipedia) (<a href=\"https:\/\/commons.wikimedia.org\/wiki\/File:DNA_replication_split_horizontal.svg?uselang=en\" target=\"_blank\" rel=\"noopener\">DNA replication split horizontal<\/a>) CC BY-SA 2.0[\/caption]\r\n\r\n[caption id=\"attachment_2571\" align=\"alignright\" width=\"470\"]<img class=\"wp-image-2571 size-full\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172346\/RNA.jpg\" alt=\"Diagram of a primer moving along the template strand of DNA.\" width=\"470\" height=\"214\" \/> Figure\u00a04. Primer and Template[\/caption]\r\n\r\n<strong>DNA polymerase<\/strong> needs an \u201canchor\u201d to start adding nucleotides: a short sequence of DNA or RNA that is complementary to the template strand will work to provide a free 3\u2032 end. This sequence is called a <em>primer\u00a0<\/em>(Figure\u00a04).\r\n\r\nHow does <strong>DNA polymerase<\/strong> know in what order to add nucleotides? Specific base pairing in DNA is the key to copying the DNA: if you know the sequence of one strand, you can use base pairing rules to build the other strand. Bases form pairs (base pairs) in a very specific way.\r\n\r\n[caption id=\"attachment_2572\" align=\"aligncenter\" width=\"451\"]<img class=\"wp-image-2572 \" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172431\/Molecular-DNA.png\" alt=\"Diagram showing the hydrogen bonds between nucleotides. Adenine is bound to thymine, and cytosine is bound to guanine. \" width=\"451\" height=\"312\" \/> Figure\u00a05. DNA chemical structure. Modification of <a href=\"https:\/\/en.wikipedia.org\/wiki\/File:DNA_chemical_structure.svg\" target=\"_blank\" rel=\"noopener\">DNA chemical structure<\/a>\u00a0by Madeleine Price Ball; CC-BY-SA-2.0[\/caption]\r\n\r\n<div class=\"textbox exercises\">\r\n<h3>Practice Questions<\/h3>\r\nTrue\/False: DNA replication requires an enzyme.\r\n\r\n[practice-area rows=\"1\"][\/practice-area]\r\n[reveal-answer q=\"527189\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"527189\"]True.\u00a0Most biological reactions rely on the enzyme to speed up the reaction. In the case of DNA\u00a0replication, this enzyme is DNA polymerase.\r\n\r\n[\/hidden-answer]\r\n\r\nWhat are the building blocks on DNA?\r\n<ol>\r\n \t<li>Deoxyribonucleotides<\/li>\r\n \t<li>Fatty acids<\/li>\r\n \t<li>Ribonucleotides<\/li>\r\n \t<li>Amino acids<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"93495\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"93495\"]Answer a. DNA is a double helix made up of two long chains of deoxyribonucleotides.\r\n\r\n[\/hidden-answer]\r\n\r\nTrue\/False: DNA replication requires energy.\r\n\r\n[practice-area rows=\"1\"][\/practice-area]\r\n[reveal-answer q=\"62103\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"62103\"]True.\u00a0Making large molecules from small subunits (anabolism) requires energy. What supplies the\u00a0energy? The building blocks themselves serve as a source of energy. As they get incorporated into\u00a0the DNA polymer, two phosphate groups are broken off to release energy, some of which is used for\u00a0making the polymer. Deoxyribonucleotides differ from nucleotides like ATP only by one missing oxygen atom.\r\n\r\n[\/hidden-answer]\r\n\r\nWe have the building blocks, a source of energy, and a catalyst. What's missing? We need instruction about the order of nucleotides in the new polymer. Which molecule provides these instructions?\r\n<ol>\r\n \t<li>Protein<\/li>\r\n \t<li>DNA<\/li>\r\n \t<li>Carbohydrate<\/li>\r\n \t<li>Lipid<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"494506\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"494506\"]Answer b.\u00a0We refer to this DNA as a template. The original information stored in the order of bases will\u00a0direct the synthesis of the new DNA via base pairing.\r\n\r\n[\/hidden-answer]\r\n\r\nThere is one more thing required by the DNA polymerase. It cannot just start making a DNA copy of the template strand; it needs a short piece of DNA or RNA with a free hydroxyl group in the right place to attach the nucleotides to. (Remember that synthesis always occurs in one direction\u2014new building blocks are added to the 3\u2032 end.) This component starts the process by giving DNA polymerase something to bind to. What might you call this short piece of nucleic acid?\r\n<ol>\r\n \t<li>A solvent<\/li>\r\n \t<li>A primer<\/li>\r\n \t<li>A converter<\/li>\r\n \t<li>A sealant<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"529681\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"529681\"]Answer b. A primer is used to start this process by giving DNA polymerase something to bind the new nucleotide to.[\/hidden-answer]\r\n\r\n<\/div>\r\nNow that you understand the basics of <strong>DNA replication<\/strong>, we can add a bit of complexity. The two strands of\u00a0DNA have to be temporarily separated from each other; this job is done by a special enzyme, <strong><em>helicase<\/em><\/strong>, that helps unwind and separate the DNA helices (Figure\u00a06). Another issue is that the DNA polymerase only works in one direction along the strand (5\u2032 to 3\u2032), but the double-stranded DNA has two strands oriented in opposite directions. This problem is solved by synthesizing the two strands slightly differently: one new strand grows continuously, the other in bits and pieces. Short fragments of RNA are used as primers for the DNA polymerase.\r\n\r\n[caption id=\"attachment_2573\" align=\"aligncenter\" width=\"1024\"]<img class=\"wp-image-2573 size-large\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172842\/DNA_replication_en.svg_-1024x498.png\" alt=\"Diagram of both the leading and lagging strands the helicase splits the two strands and a DNA polymerase travels over both strands to create complementary strands.\" width=\"1024\" height=\"498\" \/> Figure\u00a06. By Mariana Ruiz (<a href=\"https:\/\/en.wikipedia.org\/wiki\/File:DNA_replication_en.svg\" target=\"_blank\" rel=\"noopener\">DNA replication<\/a>) Public Domain[\/caption]\r\n\r\n<div class=\"textbox exercises\">\r\n<h3>Practice Questions<\/h3>\r\nWhich of these separates the two complementary strands of DNA?\r\n<ol>\r\n \t<li>DNA polymerase<\/li>\r\n \t<li>helicase<\/li>\r\n \t<li>RNA primer<\/li>\r\n \t<li>single-strand binding protein<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"197431\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"197431\"]Answer b. Helicase breaks the hydrogen bonds holding together the two strands of DNA.\r\n\r\n[\/hidden-answer]\r\n\r\nWhich of these attaches complementary bases to the template strand?\r\n<ol>\r\n \t<li>DNA polymerase<\/li>\r\n \t<li>helicase<\/li>\r\n \t<li>RNA primer<\/li>\r\n \t<li>single-strand binding protein<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"381621\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"381621\"]Answer a. DNA polymerase builds the new strand of DNA.\r\n\r\n[\/hidden-answer]\r\n\r\nWhich of these is later replaced with DNA bases?\r\n<ol>\r\n \t<li>DNA polymerase<\/li>\r\n \t<li>helicase<\/li>\r\n \t<li>RNA primer<\/li>\r\n \t<li>single-strand binding protein<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"2143\"]Show Answers[\/reveal-answer]\r\n[hidden-answer a=\"2143\"]Answer c. the RNA primer is replaced with DNA nucleotides.[\/hidden-answer]\r\n\r\n<\/div>\r\n<div class=\"textbox learning-objectives\">\r\n<h3>In Summary: Major Enzymes<\/h3>\r\nReplication in eukaryotes starts at multiple origins of replication. A primer is required to initiate synthesis, which is then extended by DNA polymerase as it adds nucleotides one by one to the growing chain. The leading strand is synthesized continuously, whereas the lagging strand is synthesized in short stretches called Okazaki fragments. The RNA primers are replaced with DNA nucleotides; the DNA remains one continuous strand by linking the DNA fragments with DNA ligase. Below is a summary table of the major enzymes addressed in this reading, listed in rough order of activity during replication.\r\n\r\n<\/div>\r\n<h2>Proofreading DNA<\/h2>\r\nDNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.\r\n\r\nMost of the mistakes during DNA replication are promptly corrected by DNA polymerase by proofreading the base that has been just added (Figure 7). In <strong>proofreading<\/strong>, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the exonuclease action of DNA pol III. Once the incorrect nucleotide has been removed, a new one will be added again.\r\n\r\n[caption id=\"attachment_1436\" align=\"aligncenter\" width=\"544\"]<img class=\"size-full wp-image-1436\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/05\/02184707\/Figure_14_06_01.jpg\" alt=\"Illustration shows DNA polymerase replicating a strand of DNA. The enzyme has accidentally inserted G opposite A, resulting in a bulge. The enzyme backs up to fix the error.\" width=\"544\" height=\"222\" \/> Figure 7. Proofreading by DNA polymerase corrects errors during replication.[\/caption]\r\n\r\nSome errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as\u00a0<strong>mismatch repair <\/strong>(Figure 8). The enzymes recognize the incorrectly added nucleotide and excise it; this is then replaced by the correct base. If this remains uncorrected, it may lead to more permanent damage. How do mismatch repair enzymes recognize which of the two bases is the incorrect one? In <em>E. coli<\/em>, after replication, the nitrogenous base adenine acquires a methyl group; the parental DNA strand will have methyl groups, whereas the newly synthesized strand lacks them. Thus, DNA polymerase is able to remove the wrongly incorporated bases from the newly synthesized, non-methylated strand. In eukaryotes, the mechanism is not very well understood, but it is believed to involve recognition of unsealed nicks in the new strand, as well as a short-term continuing association of some of the replication proteins with the new daughter strand after replication has completed.\r\n\r\n[caption id=\"attachment_4553\" align=\"aligncenter\" width=\"1237\"]<img class=\"size-full wp-image-4553\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/03\/23213100\/Figure_14_06_02ab.jpg\" alt=\"The top illustration shows a replicated DNA strand with G-T base mismatch. The bottom illustration shows the repaired DNA, which has the correct G-C base pairing.\" width=\"1237\" height=\"275\" \/> Figure 8. In mismatch repair, the incorrectly added base is detected after replication. The mismatch repair proteins detect this base and remove it from the newly synthesized strand by nuclease action. The gap is now filled with the correctly paired base.[\/caption]\r\n\r\nIn another type of repair mechanism,\u00a0<strong>nucleotide excision repair<\/strong>, enzymes replace incorrect bases by making a cut on both the 3' and 5' ends of the incorrect base (Figure 9).\r\n\r\n[caption id=\"attachment_4554\" align=\"aligncenter\" width=\"605\"]<img class=\"size-full wp-image-4554\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/03\/23213317\/Figure_14_06_03ab.jpg\" alt=\"Illustration shows a DNA strand in which a thymine dimer has formed. Excision repair enzyme cut out the section of DNA that contains the dimer so it can be replaced with normal base pairs.\" width=\"605\" height=\"143\" \/> Figure 9. Nucleotide excision repairs thymine dimers. When exposed to UV, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.[\/caption]\r\n\r\nThe segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase. This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers.\r\n<div class=\"textbox exercises\">\r\n<h3>Check Your Understanding<\/h3>\r\nIn DNA ________, the newest base is reread before another is added to ensure the DNA strand is being copied accurately.\r\n<ul>\r\n \t<li>proofreading<\/li>\r\n \t<li>verification<\/li>\r\n \t<li>copy-editing<\/li>\r\n<\/ul>\r\n<details><summary>Show Answer<\/summary>proofreading\r\n\r\n<\/details><\/div>","rendered":"<h2>What you&#8217;ll learn to do: Explain the role of complementary base pairing in the precise replication process of DNA<\/h2>\n<p>In this outcome, we&#8217;ll learn more about the precise structure of DNA and how it replicates. Watch this video for a quick introduction to this topic:<\/p>\n<p><iframe loading=\"lazy\" id=\"oembed-1\" title=\"DNA replication - 3D\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/TNKWgcFPHqw?feature=oembed&#38;rel=0\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<div class=\"textbox learning-objectives\">\n<h3>Learning Outcomes<\/h3>\n<ul>\n<li>Outline the basic steps in DNA replication<\/li>\n<li>Identify the major enzymes that play a role in DNA replication<\/li>\n<li>Identify the key proofreading processes in DNA replication<\/li>\n<\/ul>\n<\/div>\n<h2>Basics of DNA Replication<\/h2>\n<div id=\"attachment_4411\" style=\"width: 410px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4411\" class=\"wp-image-4411\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/02\/02000938\/Figure_14_03_01a.jpg\" alt=\"Illustration shows the conservative, semi-conservative, and dispersive models of DNA synthesis. In the conservative model, when DNA is replicated and both newly synthesized strands are paired together. In the semi-conservative model, each newly synthesized strand pairs with a parent strand. In the dispersive model, newly synthesized DNA is interspersed with parent DNA within both DNA strands.\" width=\"400\" height=\"404\" \/><\/p>\n<p id=\"caption-attachment-4411\" class=\"wp-caption-text\">Figure\u00a01. The three suggested models of DNA replication. Grey indicates the original DNA strands, and blue indicates newly synthesized DNA.<\/p>\n<\/div>\n<p>The elucidation of the structure of the double helix provided a hint as to how DNA divides and makes copies of itself. This model suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. What was not clear was how the replication took place. There were three models suggested: conservative, semi-conservative, and dispersive (see Figure\u00a01).<\/p>\n<p>In <strong>conservative replication<\/strong>, the parental DNA remains together, and the newly formed daughter strands are together. The <strong>semi-conservative<\/strong> method suggests that each of the two parental DNA strands act as a template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or \u201cold\u201d strand and one \u201cnew\u201d strand. In the <strong>dispersive model<\/strong>, both copies of DNA have double-stranded segments of parental DNA and newly synthesized DNA interspersed.<\/p>\n<p>Meselson and Stahl were interested in understanding how DNA replicates. They grew\u00a0<em>E. coli<\/em> for several generations in a medium containing a \u201cheavy\u201d isotope of nitrogen (<sup>15<\/sup>N) that gets incorporated into nitrogenous bases, and eventually into the DNA (Figure\u00a02).<\/p>\n<div id=\"attachment_1430\" style=\"width: 810px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1430\" class=\"size-full wp-image-1430\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/05\/02184216\/Figure_14_03_02.jpg\" alt=\"Illustration shows an experiment in which E. coli was grown initially in media containing ^{15}N nucleotides. When the DNA was extracted and run in an ultracentrifuge, a band of DNA appeared low in the tube. The culture was next placed in ^{14}N medium. After one generation, all of the DNA appeared in the middle of the tube, indicating that the DNA was a mixture of half ^{14}N and half ^{15}N DNA. After two generations, half of the DNA appeared in the middle of the tube, and half appeared higher up, indicating that half the DNA contained 50% ^{15}N, and half contained ^{14}N only. In subsequent generations, more and more of the DNA appeared in the upper, ^{14}N band.\" width=\"800\" height=\"698\" \/><\/p>\n<p id=\"caption-attachment-1430\" class=\"wp-caption-text\">Figure\u00a02. Meselson and Stahl experimented with E. coli grown first in heavy nitrogen (<sup>15<\/sup>N) then in <sup>14<\/sup>N. DNA grown in <sup>15<\/sup>N (red band) is heavier than DNA grown in <sup>14<\/sup>N (orange band), and sediments to a lower level in cesium chloride solution in an ultracentrifuge. When DNA grown in <sup>15<\/sup>N is switched to media containing <sup>14<\/sup>N, after one round of cell division the DNA sediments halfway between the <sup>15<\/sup>N and <sup>14<\/sup>N levels, indicating that it now contains fifty percent <sup>14<\/sup>N. In subsequent cell divisions, an increasing amount of DNA contains <sup>14<\/sup>N only. This data supports the semi-conservative replication model. (credit: modification of work by Mariana Ruiz Villareal)<\/p>\n<\/div>\n<p>The\u00a0<em>E. coli<\/em> culture was then shifted into medium containing <sup>14<\/sup>N and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was centrifuged at high speeds in an ultracentrifuge. Some cells were allowed to grow for one more life cycle in <sup>14<\/sup>N and spun again. During the density gradient centrifugation, the DNA is loaded into a gradient (typically a salt such as cesium chloride or sucrose) and spun at high speeds of 50,000 to 60,000 rpm. Under these circumstances, the DNA will form a band according to its density in the gradient. DNA grown in <sup>15<\/sup>N will band at a higher density position than that grown in <sup>14<\/sup>N. Meselson and Stahl noted that after one generation of growth in <sup>14<\/sup>N after they had been shifted from <sup>15<\/sup>N, the single band observed was intermediate in position in between DNA of cells grown exclusively in <sup>15<\/sup>N and <sup>14<\/sup>N. This suggested either a semi-conservative or dispersive mode of replication. The DNA harvested from cells grown for two generations in <sup>14<\/sup>N formed two bands: one DNA band was at the intermediate position between <sup>15<\/sup>N and <sup>14<\/sup>N, and the other corresponded to the band of <sup>14<\/sup>N DNA. These results could only be explained if DNA replicates in a semi-conservative manner. Therefore, the other two modes were ruled out.<\/p>\n<p>During DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or \u201cold\u201d strand. When two daughter DNA copies are formed, they have the same sequence and are divided equally into the two daughter cells.<\/p>\n<div class=\"textbox learning-objectives\">\n<h3>In Summary: Basics of DNA Replication<\/h3>\n<p>The model for DNA replication suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. In conservative replication, the parental DNA is conserved, and the daughter DNA is newly synthesized. The semi-conservative method suggests that each of the two parental DNA strands acts as template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or \u201cold\u201d strand and one \u201cnew\u201d strand. The dispersive mode suggested that the two copies of the DNA would have segments of parental DNA and newly synthesized DNA. Experimental evidence showed DNA replication is semi-conservative.<\/p>\n<\/div>\n<h2>Major Enzymes<\/h2>\n<p>The process of <strong>DNA replication<\/strong> is catalyzed by a type of enzyme called <strong>DNA polymerase<\/strong> (<em class=\"italic\">poly<\/em> meaning many, <em class=\"italic\">mer<\/em> meaning pieces, and &#8211;<em class=\"italic\">ase<\/em> meaning enzyme; so an enzyme that attaches many pieces of DNA). Observe Figure 3: the double helix of the original DNA molecule separates (blue) and new strands are made to match the separated strands. The result will be two DNA molecules, each containing an old and a new strand. Therefore, DNA replication is called semiconservative. The term <em class=\"bold\">semiconservative<\/em> refers to the fact that half of the original molecule (one of the two strands in the double helix) is \u201cconserved\u201d in the new molecule. The original strand is referred to as the <em class=\"bold\">template strand<\/em> because it provides the information, or template, for the newly synthesized strand.<\/p>\n<div id=\"attachment_2570\" style=\"width: 1034px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2570\" class=\"wp-image-2570 size-large\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172248\/DNA_replication_split_horizontal.svg_-1024x508.png\" alt=\"Stylized 3' synthesis shown, no enzymes in diagram.\" width=\"1024\" height=\"508\" \/><\/p>\n<p id=\"caption-attachment-2570\" class=\"wp-caption-text\">Figure\u00a03. By Madprime(wikipedia) (<a href=\"https:\/\/commons.wikimedia.org\/wiki\/File:DNA_replication_split_horizontal.svg?uselang=en\" target=\"_blank\" rel=\"noopener\">DNA replication split horizontal<\/a>) CC BY-SA 2.0<\/p>\n<\/div>\n<div id=\"attachment_2571\" style=\"width: 480px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2571\" class=\"wp-image-2571 size-full\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172346\/RNA.jpg\" alt=\"Diagram of a primer moving along the template strand of DNA.\" width=\"470\" height=\"214\" \/><\/p>\n<p id=\"caption-attachment-2571\" class=\"wp-caption-text\">Figure\u00a04. Primer and Template<\/p>\n<\/div>\n<p><strong>DNA polymerase<\/strong> needs an \u201canchor\u201d to start adding nucleotides: a short sequence of DNA or RNA that is complementary to the template strand will work to provide a free 3\u2032 end. This sequence is called a <em>primer\u00a0<\/em>(Figure\u00a04).<\/p>\n<p>How does <strong>DNA polymerase<\/strong> know in what order to add nucleotides? Specific base pairing in DNA is the key to copying the DNA: if you know the sequence of one strand, you can use base pairing rules to build the other strand. Bases form pairs (base pairs) in a very specific way.<\/p>\n<div id=\"attachment_2572\" style=\"width: 461px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2572\" class=\"wp-image-2572\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172431\/Molecular-DNA.png\" alt=\"Diagram showing the hydrogen bonds between nucleotides. Adenine is bound to thymine, and cytosine is bound to guanine.\" width=\"451\" height=\"312\" \/><\/p>\n<p id=\"caption-attachment-2572\" class=\"wp-caption-text\">Figure\u00a05. DNA chemical structure. Modification of <a href=\"https:\/\/en.wikipedia.org\/wiki\/File:DNA_chemical_structure.svg\" target=\"_blank\" rel=\"noopener\">DNA chemical structure<\/a>\u00a0by Madeleine Price Ball; CC-BY-SA-2.0<\/p>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Practice Questions<\/h3>\n<p>True\/False: DNA replication requires an enzyme.<\/p>\n<p><textarea aria-label=\"Your Answer\" rows=\"1\"><\/textarea><\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q527189\">Show Answer<\/span><\/p>\n<div id=\"q527189\" class=\"hidden-answer\" style=\"display: none\">True.\u00a0Most biological reactions rely on the enzyme to speed up the reaction. In the case of DNA\u00a0replication, this enzyme is DNA polymerase.<\/p>\n<\/div>\n<\/div>\n<p>What are the building blocks on DNA?<\/p>\n<ol>\n<li>Deoxyribonucleotides<\/li>\n<li>Fatty acids<\/li>\n<li>Ribonucleotides<\/li>\n<li>Amino acids<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q93495\">Show Answer<\/span><\/p>\n<div id=\"q93495\" class=\"hidden-answer\" style=\"display: none\">Answer a. DNA is a double helix made up of two long chains of deoxyribonucleotides.<\/p>\n<\/div>\n<\/div>\n<p>True\/False: DNA replication requires energy.<\/p>\n<p><textarea aria-label=\"Your Answer\" rows=\"1\"><\/textarea><\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q62103\">Show Answer<\/span><\/p>\n<div id=\"q62103\" class=\"hidden-answer\" style=\"display: none\">True.\u00a0Making large molecules from small subunits (anabolism) requires energy. What supplies the\u00a0energy? The building blocks themselves serve as a source of energy. As they get incorporated into\u00a0the DNA polymer, two phosphate groups are broken off to release energy, some of which is used for\u00a0making the polymer. Deoxyribonucleotides differ from nucleotides like ATP only by one missing oxygen atom.<\/p>\n<\/div>\n<\/div>\n<p>We have the building blocks, a source of energy, and a catalyst. What&#8217;s missing? We need instruction about the order of nucleotides in the new polymer. Which molecule provides these instructions?<\/p>\n<ol>\n<li>Protein<\/li>\n<li>DNA<\/li>\n<li>Carbohydrate<\/li>\n<li>Lipid<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q494506\">Show Answer<\/span><\/p>\n<div id=\"q494506\" class=\"hidden-answer\" style=\"display: none\">Answer b.\u00a0We refer to this DNA as a template. The original information stored in the order of bases will\u00a0direct the synthesis of the new DNA via base pairing.<\/p>\n<\/div>\n<\/div>\n<p>There is one more thing required by the DNA polymerase. It cannot just start making a DNA copy of the template strand; it needs a short piece of DNA or RNA with a free hydroxyl group in the right place to attach the nucleotides to. (Remember that synthesis always occurs in one direction\u2014new building blocks are added to the 3\u2032 end.) This component starts the process by giving DNA polymerase something to bind to. What might you call this short piece of nucleic acid?<\/p>\n<ol>\n<li>A solvent<\/li>\n<li>A primer<\/li>\n<li>A converter<\/li>\n<li>A sealant<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q529681\">Show Answer<\/span><\/p>\n<div id=\"q529681\" class=\"hidden-answer\" style=\"display: none\">Answer b. A primer is used to start this process by giving DNA polymerase something to bind the new nucleotide to.<\/div>\n<\/div>\n<\/div>\n<p>Now that you understand the basics of <strong>DNA replication<\/strong>, we can add a bit of complexity. The two strands of\u00a0DNA have to be temporarily separated from each other; this job is done by a special enzyme, <strong><em>helicase<\/em><\/strong>, that helps unwind and separate the DNA helices (Figure\u00a06). Another issue is that the DNA polymerase only works in one direction along the strand (5\u2032 to 3\u2032), but the double-stranded DNA has two strands oriented in opposite directions. This problem is solved by synthesizing the two strands slightly differently: one new strand grows continuously, the other in bits and pieces. Short fragments of RNA are used as primers for the DNA polymerase.<\/p>\n<div id=\"attachment_2573\" style=\"width: 1034px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-2573\" class=\"wp-image-2573 size-large\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/06\/02172842\/DNA_replication_en.svg_-1024x498.png\" alt=\"Diagram of both the leading and lagging strands the helicase splits the two strands and a DNA polymerase travels over both strands to create complementary strands.\" width=\"1024\" height=\"498\" \/><\/p>\n<p id=\"caption-attachment-2573\" class=\"wp-caption-text\">Figure\u00a06. By Mariana Ruiz (<a href=\"https:\/\/en.wikipedia.org\/wiki\/File:DNA_replication_en.svg\" target=\"_blank\" rel=\"noopener\">DNA replication<\/a>) Public Domain<\/p>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Practice Questions<\/h3>\n<p>Which of these separates the two complementary strands of DNA?<\/p>\n<ol>\n<li>DNA polymerase<\/li>\n<li>helicase<\/li>\n<li>RNA primer<\/li>\n<li>single-strand binding protein<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q197431\">Show Answer<\/span><\/p>\n<div id=\"q197431\" class=\"hidden-answer\" style=\"display: none\">Answer b. Helicase breaks the hydrogen bonds holding together the two strands of DNA.<\/p>\n<\/div>\n<\/div>\n<p>Which of these attaches complementary bases to the template strand?<\/p>\n<ol>\n<li>DNA polymerase<\/li>\n<li>helicase<\/li>\n<li>RNA primer<\/li>\n<li>single-strand binding protein<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q381621\">Show Answer<\/span><\/p>\n<div id=\"q381621\" class=\"hidden-answer\" style=\"display: none\">Answer a. DNA polymerase builds the new strand of DNA.<\/p>\n<\/div>\n<\/div>\n<p>Which of these is later replaced with DNA bases?<\/p>\n<ol>\n<li>DNA polymerase<\/li>\n<li>helicase<\/li>\n<li>RNA primer<\/li>\n<li>single-strand binding protein<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q2143\">Show Answers<\/span><\/p>\n<div id=\"q2143\" class=\"hidden-answer\" style=\"display: none\">Answer c. the RNA primer is replaced with DNA nucleotides.<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox learning-objectives\">\n<h3>In Summary: Major Enzymes<\/h3>\n<p>Replication in eukaryotes starts at multiple origins of replication. A primer is required to initiate synthesis, which is then extended by DNA polymerase as it adds nucleotides one by one to the growing chain. The leading strand is synthesized continuously, whereas the lagging strand is synthesized in short stretches called Okazaki fragments. The RNA primers are replaced with DNA nucleotides; the DNA remains one continuous strand by linking the DNA fragments with DNA ligase. Below is a summary table of the major enzymes addressed in this reading, listed in rough order of activity during replication.<\/p>\n<\/div>\n<h2>Proofreading DNA<\/h2>\n<p>DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.<\/p>\n<p>Most of the mistakes during DNA replication are promptly corrected by DNA polymerase by proofreading the base that has been just added (Figure 7). In <strong>proofreading<\/strong>, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the exonuclease action of DNA pol III. Once the incorrect nucleotide has been removed, a new one will be added again.<\/p>\n<div id=\"attachment_1436\" style=\"width: 554px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1436\" class=\"size-full wp-image-1436\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/110\/2016\/05\/02184707\/Figure_14_06_01.jpg\" alt=\"Illustration shows DNA polymerase replicating a strand of DNA. The enzyme has accidentally inserted G opposite A, resulting in a bulge. The enzyme backs up to fix the error.\" width=\"544\" height=\"222\" \/><\/p>\n<p id=\"caption-attachment-1436\" class=\"wp-caption-text\">Figure 7. Proofreading by DNA polymerase corrects errors during replication.<\/p>\n<\/div>\n<p>Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as\u00a0<strong>mismatch repair <\/strong>(Figure 8). The enzymes recognize the incorrectly added nucleotide and excise it; this is then replaced by the correct base. If this remains uncorrected, it may lead to more permanent damage. How do mismatch repair enzymes recognize which of the two bases is the incorrect one? In <em>E. coli<\/em>, after replication, the nitrogenous base adenine acquires a methyl group; the parental DNA strand will have methyl groups, whereas the newly synthesized strand lacks them. Thus, DNA polymerase is able to remove the wrongly incorporated bases from the newly synthesized, non-methylated strand. In eukaryotes, the mechanism is not very well understood, but it is believed to involve recognition of unsealed nicks in the new strand, as well as a short-term continuing association of some of the replication proteins with the new daughter strand after replication has completed.<\/p>\n<div id=\"attachment_4553\" style=\"width: 1247px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4553\" class=\"size-full wp-image-4553\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/03\/23213100\/Figure_14_06_02ab.jpg\" alt=\"The top illustration shows a replicated DNA strand with G-T base mismatch. The bottom illustration shows the repaired DNA, which has the correct G-C base pairing.\" width=\"1237\" height=\"275\" \/><\/p>\n<p id=\"caption-attachment-4553\" class=\"wp-caption-text\">Figure 8. In mismatch repair, the incorrectly added base is detected after replication. The mismatch repair proteins detect this base and remove it from the newly synthesized strand by nuclease action. The gap is now filled with the correctly paired base.<\/p>\n<\/div>\n<p>In another type of repair mechanism,\u00a0<strong>nucleotide excision repair<\/strong>, enzymes replace incorrect bases by making a cut on both the 3&#8242; and 5&#8242; ends of the incorrect base (Figure 9).<\/p>\n<div id=\"attachment_4554\" style=\"width: 615px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-4554\" class=\"size-full wp-image-4554\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1087\/2017\/03\/23213317\/Figure_14_06_03ab.jpg\" alt=\"Illustration shows a DNA strand in which a thymine dimer has formed. Excision repair enzyme cut out the section of DNA that contains the dimer so it can be replaced with normal base pairs.\" width=\"605\" height=\"143\" \/><\/p>\n<p id=\"caption-attachment-4554\" class=\"wp-caption-text\">Figure 9. Nucleotide excision repairs thymine dimers. When exposed to UV, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.<\/p>\n<\/div>\n<p>The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase. This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers.<\/p>\n<div class=\"textbox exercises\">\n<h3>Check Your Understanding<\/h3>\n<p>In DNA ________, the newest base is reread before another is added to ensure the DNA strand is being copied accurately.<\/p>\n<ul>\n<li>proofreading<\/li>\n<li>verification<\/li>\n<li>copy-editing<\/li>\n<\/ul>\n<details>\n<summary>Show Answer<\/summary>\n<p>proofreading<\/p>\n<\/details>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-2527\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Original<\/div><ul class=\"citation-list\"><li>Introduction to DNA Replication. <strong>Authored by<\/strong>: Shelli Carter and Lumen Learning. <strong>Provided by<\/strong>: Lumen Learning. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em><\/li><\/ul><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>Biology. <strong>Provided by<\/strong>: OpenStax CNX. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"http:\/\/cnx.org\/contents\/185cbf87-c72e-48f5-b51e-f14f21b5eabd@10.8\">http:\/\/cnx.org\/contents\/185cbf87-c72e-48f5-b51e-f14f21b5eabd@10.8<\/a>. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em>. <strong>License Terms<\/strong>: Download for free at http:\/\/cnx.org\/contents\/185cbf87-c72e-48f5-b51e-f14f21b5eabd@10.8<\/li><li>DNA Replication. <strong>Provided by<\/strong>: Open Learning Initiative. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/oli.cmu.edu\/jcourse\/workbook\/activity\/page?context=434a5f7e80020ca6000225da6a4220c9\">https:\/\/oli.cmu.edu\/jcourse\/workbook\/activity\/page?context=434a5f7e80020ca6000225da6a4220c9<\/a>. <strong>Project<\/strong>: Introduction to Biology (Open + Free). <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><\/ul><div class=\"license-attribution-dropdown-subheading\">All rights reserved content<\/div><ul class=\"citation-list\"><li>DNA replication - 3D. <strong>Authored by<\/strong>: yourgenome. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/youtu.be\/TNKWgcFPHqw\">https:\/\/youtu.be\/TNKWgcFPHqw<\/a>. <strong>License<\/strong>: <em>All Rights Reserved<\/em>. <strong>License Terms<\/strong>: Standard YouTube License<\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":17,"menu_order":19,"template":"","meta":{"_candela_citation":"[{\"type\":\"original\",\"description\":\"Introduction to DNA Replication\",\"author\":\"Shelli Carter and Lumen Learning\",\"organization\":\"Lumen Learning\",\"url\":\"\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"\"},{\"type\":\"copyrighted_video\",\"description\":\"DNA replication - 3D\",\"author\":\"yourgenome\",\"organization\":\"\",\"url\":\"https:\/\/youtu.be\/TNKWgcFPHqw\",\"project\":\"\",\"license\":\"arr\",\"license_terms\":\"Standard YouTube License\"},{\"type\":\"cc\",\"description\":\"Biology\",\"author\":\"\",\"organization\":\"OpenStax CNX\",\"url\":\"http:\/\/cnx.org\/contents\/185cbf87-c72e-48f5-b51e-f14f21b5eabd@10.8\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"Download for free at http:\/\/cnx.org\/contents\/185cbf87-c72e-48f5-b51e-f14f21b5eabd@10.8\"},{\"type\":\"cc\",\"description\":\"DNA Replication\",\"author\":\"\",\"organization\":\"Open Learning Initiative\",\"url\":\"https:\/\/oli.cmu.edu\/jcourse\/workbook\/activity\/page?context=434a5f7e80020ca6000225da6a4220c9\",\"project\":\"Introduction to Biology (Open + Free)\",\"license\":\"cc-by-nc-sa\",\"license_terms\":\"\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-2527","chapter","type-chapter","status-publish","hentry"],"part":43,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapters\/2527","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/wp\/v2\/users\/17"}],"version-history":[{"count":17,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapters\/2527\/revisions"}],"predecessor-version":[{"id":6563,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapters\/2527\/revisions\/6563"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/parts\/43"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapters\/2527\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/wp\/v2\/media?parent=2527"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/pressbooks\/v2\/chapter-type?post=2527"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/wp\/v2\/contributor?post=2527"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/ivytech-wmopen-nmbiology\/wp-json\/wp\/v2\/license?post=2527"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}