{"id":863,"date":"2018-05-03T18:35:36","date_gmt":"2018-05-03T18:35:36","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/chapter\/dna-repair\/"},"modified":"2018-06-28T12:44:10","modified_gmt":"2018-06-28T12:44:10","slug":"dna-repair","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/chapter\/dna-repair\/","title":{"raw":"DNA Repair","rendered":"DNA Repair"},"content":{"raw":"<div class=\"textbox learning-objectives\">\r\n<h3>Learning Objectives<\/h3>\r\nBy the end of this section, you will be able to do the following:\r\n<ul>\r\n \t<li>Discuss the different types of mutations in DNA<\/li>\r\n \t<li>Explain DNA repair mechanisms<\/li>\r\n<\/ul>\r\n<\/div>\r\n<p id=\"fs-id1976493\">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>\r\n<p id=\"fs-id2348700\">Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_01\">(Figure)<\/a>). In proofreading, 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 3' exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one.<\/p>\r\n\r\n<div id=\"fig-ch14_06_01\" class=\"wp-caption aligncenter\">\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"450\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183517\/Figure_14_06_01.png\" 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=\"450\" height=\"399\" \/> <strong>Figure 1. <\/strong>Proofreading by DNA polymerase corrects errors during replication.[\/caption]\r\n\r\n<\/div>\r\n<p id=\"fs-id2186525\">Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_02\">(Figure)<\/a>). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. 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>\r\n\r\n<div id=\"fig-ch14_06_02\" class=\"wp-caption aligncenter\">\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"455\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183524\/Figure_14_06_02.png\" 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=\"455\" height=\"1128\" \/> <strong>Figure 2. <\/strong>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\n<\/div>\r\n<p id=\"fs-id3000290\">Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove damaged bases rather than mismatched ones. The repair enzymes replace abnormal bases by making a cut on both the 3' and 5' ends of the damaged base (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_03\">(Figure)<\/a>). 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>\r\n\r\n<div id=\"fig-ch14_06_03\" class=\"wp-caption aligncenter\">\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"200\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183527\/Figure_14_06_03.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=\"200\" height=\"325\" \/> <strong>Figure 3. <\/strong>Nucleotide excision repairs thymine dimers. When exposed to UV light, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.[\/caption]\r\n\r\n<\/div>\r\n<p id=\"fs-id2078153\">A well-studied example of mistakes not being corrected is seen in people suffering from xeroderma pigmentosa (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_04\">(Figure)<\/a>). Affected individuals have skin that is highly sensitive to UV rays from the sun. When individuals are exposed to UV light, pyrimidine dimers, especially those of thymine, are formed; people with xeroderma pigmentosa are not able to repair the damage. These are not repaired because of a defect in the nucleotide excision repair enzymes, whereas in normal individuals, the thymine dimers are excised and the defect is corrected. The thymine dimers distort the structure of the DNA double helix, and this may cause problems during DNA replication. People with xeroderma pigmentosa may have a higher risk of contracting skin cancer than those who don't have the condition.<\/p>\r\n\r\n<div id=\"fig-ch14_06_04\" class=\"wp-caption aligncenter\">\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"320\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183531\/Figure_14_06_04.jpg\" alt=\"Photo shows a person with mottled skin lesions that result from xermoderma pigmentosa.\" width=\"320\" height=\"1071\" \/> <strong>Figure 4. <\/strong>Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired. Exposure to sunlight results in skin lesions. (credit: James Halpern et al.)[\/caption]\r\n\r\n<\/div>\r\n<p id=\"fs-id1310247\">Errors during DNA replication are not the only reason why mutations arise in DNA. Mutations, variations in the nucleotide sequence of a genome, can also occur because of damage to DNA. Such mutations may be of two types: induced or spontaneous. Induced mutations are those that result from an exposure to chemicals, UV rays, x-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent; they are a result of natural reactions taking place within the body.<\/p>\r\nMutations may have a wide range of effects. Point mutations are those mutations that affect a single base pair. The most common nucleotide mutations are substitutions, in which one base is replaced by another. These substitutions can be of two types, either transitions or transversions. Transition substitution refers to a purine or pyrimidine being replaced by a base of the same kind; for example, a purine such as adenine may be replaced by the purine guanine. Transversion substitution refers to a purine being replaced by a pyrimidine, or vice versa; for example, cytosine, a pyrimidine, is replaced by adenine, a purine. Some point mutations are not expressed; these are known as silent mutations. Silent mutations are usually due to a substitution in the third base of a codon, which often represents the same amino acid as the original codon. Other point mutations can result in the replacement of one amino acid by another, which may alter the function of the protein. Point mutations that generate a stop codon can terminate a protein early.\r\n<p id=\"fs-id1378727\">Some mutations can result in an increased number of copies of the same codon. These are called trinucleotide repeat expansions and result in repeated regions of the same amino acid. Mutations can also be the result of the addition of a base, known as an insertion, or the removal of a base, also known as deletion. If an insertion or deletion results in the alteration of the translational reading frame (a frameshift mutation), the resultant protein is usually nonfunctional. Sometimes a piece of DNA from one chromosome may get translocated to another chromosome or to another region of the same chromosome; this is also known as translocation. These mutation types are shown in <a class=\"autogenerated-content\" href=\"#fig-ch14_06_05\">(Figure)<\/a>.<\/p>\r\n\r\n<div id=\"fs-id2046784\" class=\"art-connection textbox examples\">\r\n<h3>Art Connection<\/h3>\r\n<div id=\"fig-ch14_06_05\" class=\"wp-caption aligncenter\">\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"325\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183535\/Figure_14_06_05.png\" alt=\"Illustration shows different types of point mutations that result from a single amino acid substitution. In a silent mutation, no change in the amino acid sequence occurs. In a missense mutation, one amino acid is substituted for another. In a nonsense mutation, a stop codon is substituted for an amino acid. In a frameshift mutation, one or more bases is added or deleted, resulting in a change in the reading frame.\" width=\"325\" height=\"599\" \/> <strong>Figure 5. <\/strong>Mutations can lead to changes in the protein sequence encoded by the DNA.[\/caption]\r\n\r\n<\/div>\r\n<p id=\"fs-id1813148\">A frameshift mutation that results in the insertion of three nucleotides is often less deleterious than a mutation that results in the insertion of one nucleotide. Why?<\/p>\r\n\r\n<\/div>\r\n<p id=\"fs-id2936137\">Mutations in repair genes have been known to cause cancer. Many mutated repair genes have been implicated in certain forms of pancreatic cancer, colon cancer, and colorectal cancer. Mutations can affect either somatic cells or germ cells. If many mutations accumulate in a somatic cell, they may lead to problems such as the uncontrolled cell division observed in cancer. If a mutation takes place in germ cells, the mutation will be passed on to the next generation, as in the case of hemophilia and xeroderma pigmentosa.<\/p>\r\n\r\n<div id=\"fs-id2065835\" class=\"summary textbox key-takeaways\">\r\n<h3>Section Summary<\/h3>\r\n<p id=\"fs-id1242469\">DNA polymerase can make mistakes while adding nucleotides. It edits the DNA by proofreading every newly added base. Incorrect bases are removed and replaced by the correct base before proceeding with elongation. Most mistakes are corrected during replication, although when this does not happen, the mismatch repair mechanism is employed. Mismatch repair enzymes recognize the wrongly incorporated base and excise it from the DNA, replacing it with the correct base. In yet another type of repair, nucleotide excision repair, a damaged base is removed along with a few bases on the 5' and 3' end, and these are replaced by copying the template with the help of DNA polymerase. The ends of the newly synthesized fragment are attached to the rest of the DNA using DNA ligase, which creates a phosphodiester bond.<\/p>\r\n<p id=\"fs-id2595588\">Most mistakes are corrected, and if they are not, they may result in a mutation, defined as a permanent change in the DNA sequence. Mutations can be of many types, such as substitution, deletion, insertion, and trinucleotide repeat expansions. Mutations in repair genes may lead to serious consequences such as cancer. Mutations can be induced or may occur spontaneously.<\/p>\r\n\r\n<\/div>\r\n<div id=\"fs-idp123953472\" class=\"art-exercise\">\r\n<h3>Art Connections<\/h3>\r\n<div id=\"fs-idp163052304\">\r\n<div id=\"fs-idp152472016\">\r\n<p id=\"fs-idp131842896\"><a class=\"autogenerated-content\" href=\"#fig-ch14_06_05\">(Figure)<\/a> A frameshift mutation that results in the insertion of three nucleotides is often less deleterious than a mutation that results in the insertion of one nucleotide. Why?<\/p>\r\n\r\n<\/div>\r\n<div id=\"fs-idp122564624\">\r\n<p id=\"fs-idp74157744\">[reveal-answer q=\"910520\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"910520\"]<\/p>\r\n<a href=\"#fig-ch14_06_05\">(Figure)<\/a> If three nucleotides are added, one additional amino acid will be incorporated into the protein chain, but the reading frame wont shift.[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"fs-id2681952\" class=\"multiple-choice textbox exercises\">\r\n<h3>Review Questions<\/h3>\r\n<div id=\"fs-id1951731\">\r\n<div id=\"fs-id1477381\">\r\n\r\nDuring proofreading, which of the following enzymes reads the DNA?\r\n<ol id=\"fs-id2781180\" type=\"a\">\r\n \t<li>primase<\/li>\r\n \t<li>topoisomerase<\/li>\r\n \t<li>DNA pol<\/li>\r\n \t<li>helicase<\/li>\r\n<\/ol>\r\n<\/div>\r\n[reveal-answer q=\"fs-id2750351\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"fs-id2750351\"]\r\n<div id=\"fs-id2750351\">\r\n<p id=\"fs-id1477929\">C<\/p>\r\n\r\n<\/div>\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<div id=\"fs-id1414909\">\r\n<div id=\"fs-id2415145\">\r\n<p id=\"fs-id2073382\">The initial mechanism for repairing nucleotide errors in DNA is ________.<\/p>\r\n\r\n<ol type=\"a\">\r\n \t<li>mismatch repair<\/li>\r\n \t<li>DNA polymerase proofreading<\/li>\r\n \t<li>nucleotide excision repair<\/li>\r\n \t<li>thymine dimers<\/li>\r\n<\/ol>\r\n<\/div>\r\n[reveal-answer q=\"fs-id1837280\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"fs-id1837280\"]\r\n<div id=\"fs-id1837280\">\r\n<p id=\"fs-id2051151\">B<\/p>\r\n\r\n<\/div>\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<div id=\"eip-338\">\r\n<div id=\"eip-963\">\r\n<p id=\"eip-790\">A scientist creates fruit fly larvae with a mutation that eliminates the exonuclease function of DNA pol III. Which prediction about the mutational load in the adult fruit flies is most likely to be correct?<\/p>\r\n\r\n<ol id=\"eip-275\" type=\"a\">\r\n \t<li>The adults with the DNA pol III mutation will have significantly more mutations than average.<\/li>\r\n \t<li>The adults with the DNA pol III mutation will have slightly more mutations than average.<\/li>\r\n \t<li>The adults with the DNA pol III mutation will have the same number of mutations as average.<\/li>\r\n \t<li>The adults with the DNA pol III mutation will have fewer mutations than average.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<div id=\"eip-79\">\r\n\r\n[reveal-answer q=\"982269\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"982269\"]\r\n\r\nB[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"fs-id811872\" class=\"free-response textbox exercises\">\r\n<h3>Free Response<\/h3>\r\n<div id=\"fs-id2008893\">\r\n<div id=\"fs-id2763212\">\r\n<p id=\"fs-id3044550\">What is the consequence of mutation of a mismatch repair enzyme? How will this affect the function of a gene?<\/p>\r\n\r\n<\/div>\r\n[reveal-answer q=\"fs-id1385923\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"fs-id1385923\"]\r\n<div id=\"fs-id1385923\">\r\n\r\nMutations are not repaired, as in the case of xeroderma pigmentosa. Gene function may be affected or it may not be expressed.\r\n\r\n<\/div>\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<div id=\"eip-546\">\r\n<div id=\"eip-994\">\r\n<p id=\"eip-335\">An adult with a history of tanning has his genome sequenced. The beginning of a protein-coding region of his DNA reads ATGGGGATATGGCAT. If the protein-coding region of a healthy adult reads ATGGGGATATGAGCAT, identify the site and type of mutation.<\/p>\r\n\r\n<\/div>\r\n<div id=\"eip-563\">\r\n\r\n[reveal-answer q=\"823300\"]Show Solution[\/reveal-answer]\r\n[hidden-answer a=\"823300\"]\r\n\r\nThis is a frameshift mutation with a deletion of an \u201cA\u201d in the 12<sup>th<\/sup> position of the coding region.\r\n<ul id=\"eip-287\">\r\n \t<li>Patient: ATGGGGATATGGCAT<\/li>\r\n \t<li>Normal: ATGGGGATATGAGCAT<\/li>\r\n<\/ul>\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div class=\"textbox shaded\">\r\n<h3>Glossary<\/h3>\r\n<dl id=\"fs-id1719569\">\r\n \t<dt>induced mutation<\/dt>\r\n \t<dd id=\"fs-id1769884\">mutation that results from exposure to chemicals or environmental agents<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id2199830\">\r\n \t<dt>mutation<\/dt>\r\n \t<dd id=\"fs-id2905083\">variation in the nucleotide sequence of a genome<\/dd>\r\n<\/dl>\r\n<dl>\r\n \t<dt>mismatch repair<\/dt>\r\n \t<dd id=\"fs-id2308429\">type of repair mechanism in which mismatched bases are removed after replication<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id2013508\">\r\n \t<dt>nucleotide excision repair<\/dt>\r\n \t<dd id=\"fs-id2689408\">type of DNA repair mechanism in which the wrong base, along with a few nucleotides upstream or downstream, are removed<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id1770263\">\r\n \t<dt>proofreading<\/dt>\r\n \t<dd id=\"fs-id1785888\">function of DNA pol in which it reads the newly added base before adding the next one<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id1560334\">\r\n \t<dt>point mutation<\/dt>\r\n \t<dd id=\"fs-id2186102\">mutation that affects a single base<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id1582545\">\r\n \t<dt>silent mutation<\/dt>\r\n \t<dd id=\"fs-id1595608\">mutation that is not expressed<\/dd>\r\n<\/dl>\r\n<dl id=\"fs-id1412270\">\r\n \t<dt>spontaneous mutation<\/dt>\r\n \t<dd>mutation that takes place in the cells as a result of chemical reactions taking place naturally without exposure to any external agent<\/dd>\r\n<\/dl>\r\n<dl>\r\n \t<dt>transition substitution<\/dt>\r\n \t<dd id=\"fs-id1693442\">when a purine is replaced with a purine or a pyrimidine is replaced with another pyrimidine<\/dd>\r\n<\/dl>\r\n<dl>\r\n \t<dt>transversion substitution<\/dt>\r\n \t<dd id=\"fs-id1506870\">when a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine<\/dd>\r\n<\/dl>\r\n<\/div>","rendered":"<div class=\"textbox learning-objectives\">\n<h3>Learning Objectives<\/h3>\n<p>By the end of this section, you will be able to do the following:<\/p>\n<ul>\n<li>Discuss the different types of mutations in DNA<\/li>\n<li>Explain DNA repair mechanisms<\/li>\n<\/ul>\n<\/div>\n<p id=\"fs-id1976493\">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 id=\"fs-id2348700\">Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_01\">(Figure)<\/a>). In proofreading, 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 3&#8242; exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one.<\/p>\n<div id=\"fig-ch14_06_01\" class=\"wp-caption aligncenter\">\n<div style=\"width: 460px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183517\/Figure_14_06_01.png\" 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=\"450\" height=\"399\" \/><\/p>\n<p class=\"wp-caption-text\"><strong>Figure 1. <\/strong>Proofreading by DNA polymerase corrects errors during replication.<\/p>\n<\/div>\n<\/div>\n<p id=\"fs-id2186525\">Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_02\">(Figure)<\/a>). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. 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=\"fig-ch14_06_02\" class=\"wp-caption aligncenter\">\n<div style=\"width: 465px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183524\/Figure_14_06_02.png\" 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=\"455\" height=\"1128\" \/><\/p>\n<p class=\"wp-caption-text\"><strong>Figure 2. <\/strong>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<\/div>\n<p id=\"fs-id3000290\">Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove damaged bases rather than mismatched ones. The repair enzymes replace abnormal bases by making a cut on both the 3&#8242; and 5&#8242; ends of the damaged base (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_03\">(Figure)<\/a>). 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 id=\"fig-ch14_06_03\" class=\"wp-caption aligncenter\">\n<div style=\"width: 210px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183527\/Figure_14_06_03.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=\"200\" height=\"325\" \/><\/p>\n<p class=\"wp-caption-text\"><strong>Figure 3. <\/strong>Nucleotide excision repairs thymine dimers. When exposed to UV light, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.<\/p>\n<\/div>\n<\/div>\n<p id=\"fs-id2078153\">A well-studied example of mistakes not being corrected is seen in people suffering from xeroderma pigmentosa (<a class=\"autogenerated-content\" href=\"#fig-ch14_06_04\">(Figure)<\/a>). Affected individuals have skin that is highly sensitive to UV rays from the sun. When individuals are exposed to UV light, pyrimidine dimers, especially those of thymine, are formed; people with xeroderma pigmentosa are not able to repair the damage. These are not repaired because of a defect in the nucleotide excision repair enzymes, whereas in normal individuals, the thymine dimers are excised and the defect is corrected. The thymine dimers distort the structure of the DNA double helix, and this may cause problems during DNA replication. People with xeroderma pigmentosa may have a higher risk of contracting skin cancer than those who don&#8217;t have the condition.<\/p>\n<div id=\"fig-ch14_06_04\" class=\"wp-caption aligncenter\">\n<div style=\"width: 330px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183531\/Figure_14_06_04.jpg\" alt=\"Photo shows a person with mottled skin lesions that result from xermoderma pigmentosa.\" width=\"320\" height=\"1071\" \/><\/p>\n<p class=\"wp-caption-text\"><strong>Figure 4. <\/strong>Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired. Exposure to sunlight results in skin lesions. (credit: James Halpern et al.)<\/p>\n<\/div>\n<\/div>\n<p id=\"fs-id1310247\">Errors during DNA replication are not the only reason why mutations arise in DNA. Mutations, variations in the nucleotide sequence of a genome, can also occur because of damage to DNA. Such mutations may be of two types: induced or spontaneous. Induced mutations are those that result from an exposure to chemicals, UV rays, x-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent; they are a result of natural reactions taking place within the body.<\/p>\n<p>Mutations may have a wide range of effects. Point mutations are those mutations that affect a single base pair. The most common nucleotide mutations are substitutions, in which one base is replaced by another. These substitutions can be of two types, either transitions or transversions. Transition substitution refers to a purine or pyrimidine being replaced by a base of the same kind; for example, a purine such as adenine may be replaced by the purine guanine. Transversion substitution refers to a purine being replaced by a pyrimidine, or vice versa; for example, cytosine, a pyrimidine, is replaced by adenine, a purine. Some point mutations are not expressed; these are known as silent mutations. Silent mutations are usually due to a substitution in the third base of a codon, which often represents the same amino acid as the original codon. Other point mutations can result in the replacement of one amino acid by another, which may alter the function of the protein. Point mutations that generate a stop codon can terminate a protein early.<\/p>\n<p id=\"fs-id1378727\">Some mutations can result in an increased number of copies of the same codon. These are called trinucleotide repeat expansions and result in repeated regions of the same amino acid. Mutations can also be the result of the addition of a base, known as an insertion, or the removal of a base, also known as deletion. If an insertion or deletion results in the alteration of the translational reading frame (a frameshift mutation), the resultant protein is usually nonfunctional. Sometimes a piece of DNA from one chromosome may get translocated to another chromosome or to another region of the same chromosome; this is also known as translocation. These mutation types are shown in <a class=\"autogenerated-content\" href=\"#fig-ch14_06_05\">(Figure)<\/a>.<\/p>\n<div id=\"fs-id2046784\" class=\"art-connection textbox examples\">\n<h3>Art Connection<\/h3>\n<div id=\"fig-ch14_06_05\" class=\"wp-caption aligncenter\">\n<div style=\"width: 335px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3206\/2018\/05\/03183535\/Figure_14_06_05.png\" alt=\"Illustration shows different types of point mutations that result from a single amino acid substitution. In a silent mutation, no change in the amino acid sequence occurs. In a missense mutation, one amino acid is substituted for another. In a nonsense mutation, a stop codon is substituted for an amino acid. In a frameshift mutation, one or more bases is added or deleted, resulting in a change in the reading frame.\" width=\"325\" height=\"599\" \/><\/p>\n<p class=\"wp-caption-text\"><strong>Figure 5. <\/strong>Mutations can lead to changes in the protein sequence encoded by the DNA.<\/p>\n<\/div>\n<\/div>\n<p id=\"fs-id1813148\">A frameshift mutation that results in the insertion of three nucleotides is often less deleterious than a mutation that results in the insertion of one nucleotide. Why?<\/p>\n<\/div>\n<p id=\"fs-id2936137\">Mutations in repair genes have been known to cause cancer. Many mutated repair genes have been implicated in certain forms of pancreatic cancer, colon cancer, and colorectal cancer. Mutations can affect either somatic cells or germ cells. If many mutations accumulate in a somatic cell, they may lead to problems such as the uncontrolled cell division observed in cancer. If a mutation takes place in germ cells, the mutation will be passed on to the next generation, as in the case of hemophilia and xeroderma pigmentosa.<\/p>\n<div id=\"fs-id2065835\" class=\"summary textbox key-takeaways\">\n<h3>Section Summary<\/h3>\n<p id=\"fs-id1242469\">DNA polymerase can make mistakes while adding nucleotides. It edits the DNA by proofreading every newly added base. Incorrect bases are removed and replaced by the correct base before proceeding with elongation. Most mistakes are corrected during replication, although when this does not happen, the mismatch repair mechanism is employed. Mismatch repair enzymes recognize the wrongly incorporated base and excise it from the DNA, replacing it with the correct base. In yet another type of repair, nucleotide excision repair, a damaged base is removed along with a few bases on the 5&#8242; and 3&#8242; end, and these are replaced by copying the template with the help of DNA polymerase. The ends of the newly synthesized fragment are attached to the rest of the DNA using DNA ligase, which creates a phosphodiester bond.<\/p>\n<p id=\"fs-id2595588\">Most mistakes are corrected, and if they are not, they may result in a mutation, defined as a permanent change in the DNA sequence. Mutations can be of many types, such as substitution, deletion, insertion, and trinucleotide repeat expansions. Mutations in repair genes may lead to serious consequences such as cancer. Mutations can be induced or may occur spontaneously.<\/p>\n<\/div>\n<div id=\"fs-idp123953472\" class=\"art-exercise\">\n<h3>Art Connections<\/h3>\n<div id=\"fs-idp163052304\">\n<div id=\"fs-idp152472016\">\n<p id=\"fs-idp131842896\"><a class=\"autogenerated-content\" href=\"#fig-ch14_06_05\">(Figure)<\/a> A frameshift mutation that results in the insertion of three nucleotides is often less deleterious than a mutation that results in the insertion of one nucleotide. Why?<\/p>\n<\/div>\n<div id=\"fs-idp122564624\">\n<p id=\"fs-idp74157744\">\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q910520\">Show Solution<\/span><\/p>\n<div id=\"q910520\" class=\"hidden-answer\" style=\"display: none\">\n<p><a href=\"#fig-ch14_06_05\">(Figure)<\/a> If three nucleotides are added, one additional amino acid will be incorporated into the protein chain, but the reading frame wont shift.<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"fs-id2681952\" class=\"multiple-choice textbox exercises\">\n<h3>Review Questions<\/h3>\n<div id=\"fs-id1951731\">\n<div id=\"fs-id1477381\">\n<p>During proofreading, which of the following enzymes reads the DNA?<\/p>\n<ol id=\"fs-id2781180\" type=\"a\">\n<li>primase<\/li>\n<li>topoisomerase<\/li>\n<li>DNA pol<\/li>\n<li>helicase<\/li>\n<\/ol>\n<\/div>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"qfs-id2750351\">Show Solution<\/span><\/p>\n<div id=\"qfs-id2750351\" class=\"hidden-answer\" style=\"display: none\">\n<div id=\"fs-id2750351\">\n<p id=\"fs-id1477929\">C<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"fs-id1414909\">\n<div id=\"fs-id2415145\">\n<p id=\"fs-id2073382\">The initial mechanism for repairing nucleotide errors in DNA is ________.<\/p>\n<ol type=\"a\">\n<li>mismatch repair<\/li>\n<li>DNA polymerase proofreading<\/li>\n<li>nucleotide excision repair<\/li>\n<li>thymine dimers<\/li>\n<\/ol>\n<\/div>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"qfs-id1837280\">Show Solution<\/span><\/p>\n<div id=\"qfs-id1837280\" class=\"hidden-answer\" style=\"display: none\">\n<div id=\"fs-id1837280\">\n<p id=\"fs-id2051151\">B<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"eip-338\">\n<div id=\"eip-963\">\n<p id=\"eip-790\">A scientist creates fruit fly larvae with a mutation that eliminates the exonuclease function of DNA pol III. Which prediction about the mutational load in the adult fruit flies is most likely to be correct?<\/p>\n<ol id=\"eip-275\" type=\"a\">\n<li>The adults with the DNA pol III mutation will have significantly more mutations than average.<\/li>\n<li>The adults with the DNA pol III mutation will have slightly more mutations than average.<\/li>\n<li>The adults with the DNA pol III mutation will have the same number of mutations as average.<\/li>\n<li>The adults with the DNA pol III mutation will have fewer mutations than average.<\/li>\n<\/ol>\n<\/div>\n<div id=\"eip-79\">\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q982269\">Show Solution<\/span><\/p>\n<div id=\"q982269\" class=\"hidden-answer\" style=\"display: none\">\n<p>B<\/p><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"fs-id811872\" class=\"free-response textbox exercises\">\n<h3>Free Response<\/h3>\n<div id=\"fs-id2008893\">\n<div id=\"fs-id2763212\">\n<p id=\"fs-id3044550\">What is the consequence of mutation of a mismatch repair enzyme? How will this affect the function of a gene?<\/p>\n<\/div>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"qfs-id1385923\">Show Solution<\/span><\/p>\n<div id=\"qfs-id1385923\" class=\"hidden-answer\" style=\"display: none\">\n<div id=\"fs-id1385923\">\n<p>Mutations are not repaired, as in the case of xeroderma pigmentosa. Gene function may be affected or it may not be expressed.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"eip-546\">\n<div id=\"eip-994\">\n<p id=\"eip-335\">An adult with a history of tanning has his genome sequenced. The beginning of a protein-coding region of his DNA reads ATGGGGATATGGCAT. If the protein-coding region of a healthy adult reads ATGGGGATATGAGCAT, identify the site and type of mutation.<\/p>\n<\/div>\n<div id=\"eip-563\">\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q823300\">Show Solution<\/span><\/p>\n<div id=\"q823300\" class=\"hidden-answer\" style=\"display: none\">\n<p>This is a frameshift mutation with a deletion of an \u201cA\u201d in the 12<sup>th<\/sup> position of the coding region.<\/p>\n<ul id=\"eip-287\">\n<li>Patient: ATGGGGATATGGCAT<\/li>\n<li>Normal: ATGGGGATATGAGCAT<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox shaded\">\n<h3>Glossary<\/h3>\n<dl id=\"fs-id1719569\">\n<dt>induced mutation<\/dt>\n<dd id=\"fs-id1769884\">mutation that results from exposure to chemicals or environmental agents<\/dd>\n<\/dl>\n<dl id=\"fs-id2199830\">\n<dt>mutation<\/dt>\n<dd id=\"fs-id2905083\">variation in the nucleotide sequence of a genome<\/dd>\n<\/dl>\n<dl>\n<dt>mismatch repair<\/dt>\n<dd id=\"fs-id2308429\">type of repair mechanism in which mismatched bases are removed after replication<\/dd>\n<\/dl>\n<dl id=\"fs-id2013508\">\n<dt>nucleotide excision repair<\/dt>\n<dd id=\"fs-id2689408\">type of DNA repair mechanism in which the wrong base, along with a few nucleotides upstream or downstream, are removed<\/dd>\n<\/dl>\n<dl id=\"fs-id1770263\">\n<dt>proofreading<\/dt>\n<dd id=\"fs-id1785888\">function of DNA pol in which it reads the newly added base before adding the next one<\/dd>\n<\/dl>\n<dl id=\"fs-id1560334\">\n<dt>point mutation<\/dt>\n<dd id=\"fs-id2186102\">mutation that affects a single base<\/dd>\n<\/dl>\n<dl id=\"fs-id1582545\">\n<dt>silent mutation<\/dt>\n<dd id=\"fs-id1595608\">mutation that is not expressed<\/dd>\n<\/dl>\n<dl id=\"fs-id1412270\">\n<dt>spontaneous mutation<\/dt>\n<dd>mutation that takes place in the cells as a result of chemical reactions taking place naturally without exposure to any external agent<\/dd>\n<\/dl>\n<dl>\n<dt>transition substitution<\/dt>\n<dd id=\"fs-id1693442\">when a purine is replaced with a purine or a pyrimidine is replaced with another pyrimidine<\/dd>\n<\/dl>\n<dl>\n<dt>transversion substitution<\/dt>\n<dd id=\"fs-id1506870\">when a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine<\/dd>\n<\/dl>\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-863\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>Biology 2e. <strong>Provided by<\/strong>: OpenStax. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/openstax.org\/details\/books\/biology-2e\">https:\/\/openstax.org\/details\/books\/biology-2e<\/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\/8d50a0af-948b-4204-a71d-4826cba765b8@8.19<\/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":311,"menu_order":7,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"Biology 2e\",\"author\":\"\",\"organization\":\"OpenStax\",\"url\":\"https:\/\/openstax.org\/details\/books\/biology-2e\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"Download for free at http:\/\/cnx.org\/contents\/8d50a0af-948b-4204-a71d-4826cba765b8@8.19\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-863","chapter","type-chapter","status-publish","hentry"],"part":835,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapters\/863","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/wp\/v2\/users\/311"}],"version-history":[{"count":3,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapters\/863\/revisions"}],"predecessor-version":[{"id":2517,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapters\/863\/revisions\/2517"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/parts\/835"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapters\/863\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/wp\/v2\/media?parent=863"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/pressbooks\/v2\/chapter-type?post=863"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/wp\/v2\/contributor?post=863"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-osbiology2e\/wp-json\/wp\/v2\/license?post=863"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}