A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands
Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the laggin...
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Veröffentlicht in: | Molecular cell 2015-07, Vol.59 (2), p.163-175 |
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description | Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.
[Display omitted]
•Polδ-generated errors occur on both the leading and lagging DNA strands•Polδ errors are removed by mismatch repair, Polε exonuclease, and Exo1•Polδ replicates both the leading and lagging DNA strands•Polε does not replicate the leading strand
The current model of eukaryotic DNA replication suggests that DNA polymerase (Pol)ε primarily replicates the leading strand while Polδ replicates the lagging strand. Johnson et al. provide genetic evidence that Polδ replicates both strands, while Polε’s proofreading activity is important for removing Polδ-generated errors from the leading strand. |
doi_str_mv | 10.1016/j.molcel.2015.05.038 |
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[Display omitted]
•Polδ-generated errors occur on both the leading and lagging DNA strands•Polδ errors are removed by mismatch repair, Polε exonuclease, and Exo1•Polδ replicates both the leading and lagging DNA strands•Polε does not replicate the leading strand
The current model of eukaryotic DNA replication suggests that DNA polymerase (Pol)ε primarily replicates the leading strand while Polδ replicates the lagging strand. Johnson et al. provide genetic evidence that Polδ replicates both strands, while Polε’s proofreading activity is important for removing Polδ-generated errors from the leading strand.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2015.05.038</identifier><identifier>PMID: 26145172</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Substitution ; Base Pair Mismatch ; DNA Polymerase II - genetics ; DNA Polymerase II - metabolism ; DNA Polymerase III - genetics ; DNA Polymerase III - metabolism ; DNA Replication ; DNA, Fungal - genetics ; DNA, Fungal - metabolism ; Exodeoxyribonucleases - genetics ; Exodeoxyribonucleases - metabolism ; Genome, Fungal ; Mutagenesis, Site-Directed ; Mutation ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism</subject><ispartof>Molecular cell, 2015-07, Vol.59 (2), p.163-175</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><rights>2015 Published by Elsevier Inc. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-e66d84b677f8a2793815bc7476e8c0e29680f2fac23b7d8ba69daf07827b0ec33</citedby><cites>FETCH-LOGICAL-c533t-e66d84b677f8a2793815bc7476e8c0e29680f2fac23b7d8ba69daf07827b0ec33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molcel.2015.05.038$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,782,786,887,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26145172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Robert E.</creatorcontrib><creatorcontrib>Klassen, Roland</creatorcontrib><creatorcontrib>Prakash, Louise</creatorcontrib><creatorcontrib>Prakash, Satya</creatorcontrib><title>A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.
[Display omitted]
•Polδ-generated errors occur on both the leading and lagging DNA strands•Polδ errors are removed by mismatch repair, Polε exonuclease, and Exo1•Polδ replicates both the leading and lagging DNA strands•Polε does not replicate the leading strand
The current model of eukaryotic DNA replication suggests that DNA polymerase (Pol)ε primarily replicates the leading strand while Polδ replicates the lagging strand. Johnson et al. provide genetic evidence that Polδ replicates both strands, while Polε’s proofreading activity is important for removing Polδ-generated errors from the leading strand.</description><subject>Amino Acid Substitution</subject><subject>Base Pair Mismatch</subject><subject>DNA Polymerase II - genetics</subject><subject>DNA Polymerase II - metabolism</subject><subject>DNA Polymerase III - genetics</subject><subject>DNA Polymerase III - metabolism</subject><subject>DNA Replication</subject><subject>DNA, Fungal - genetics</subject><subject>DNA, Fungal - metabolism</subject><subject>Exodeoxyribonucleases - genetics</subject><subject>Exodeoxyribonucleases - metabolism</subject><subject>Genome, Fungal</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Udtq4zAUFEvLprc_WIoe9yWpJNuS_FLI9g7pbknbtwUhy8eJgm2lklPof_U7-k2VSXp7KRzQ4WjOjDSD0C9KRpRQfrQYNa42UI8YodmIxErkD7RDSS6GKeXp1qZngmcDtBvCghCaZjL_iQaMx44KtoP-j_G1XjiPp64G7Cp8-neMb1z91IDXAfDLM7YtnsKytkZ31rU95o_r5ribA56ALm07w7ot8UTPZn3fE9x2Po7CPtqudB3gYHPuofvzs7uTy-Hk38XVyXgyNFmSdEPgvJRpwYWopGYiTyTNCiNSwUEaAiznklSs0oYlhShloXle6ooIyURBwCTJHjpe8y5XRQOlgTbq12rpbaP9k3Laqq83rZ2rmXtUvQkyyyPB7w2Bdw8rCJ1qbIje1roFtwqK8lwwmmc8jdB0DTXeheChepehRPXBqIVaB6P6YBSJlci4dvj5ie9Lb0l8_AGiUY8WvArGQmugtB5Mp0pnv1d4BSxjoSQ</recordid><startdate>20150716</startdate><enddate>20150716</enddate><creator>Johnson, Robert E.</creator><creator>Klassen, Roland</creator><creator>Prakash, Louise</creator><creator>Prakash, Satya</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150716</creationdate><title>A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands</title><author>Johnson, Robert E. ; Klassen, Roland ; Prakash, Louise ; Prakash, Satya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-e66d84b677f8a2793815bc7476e8c0e29680f2fac23b7d8ba69daf07827b0ec33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amino Acid Substitution</topic><topic>Base Pair Mismatch</topic><topic>DNA Polymerase II - genetics</topic><topic>DNA Polymerase II - metabolism</topic><topic>DNA Polymerase III - genetics</topic><topic>DNA Polymerase III - metabolism</topic><topic>DNA Replication</topic><topic>DNA, Fungal - genetics</topic><topic>DNA, Fungal - metabolism</topic><topic>Exodeoxyribonucleases - genetics</topic><topic>Exodeoxyribonucleases - metabolism</topic><topic>Genome, Fungal</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnson, Robert E.</creatorcontrib><creatorcontrib>Klassen, Roland</creatorcontrib><creatorcontrib>Prakash, Louise</creatorcontrib><creatorcontrib>Prakash, Satya</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnson, Robert E.</au><au>Klassen, Roland</au><au>Prakash, Louise</au><au>Prakash, Satya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2015-07-16</date><risdate>2015</risdate><volume>59</volume><issue>2</issue><spage>163</spage><epage>175</epage><pages>163-175</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.
[Display omitted]
•Polδ-generated errors occur on both the leading and lagging DNA strands•Polδ errors are removed by mismatch repair, Polε exonuclease, and Exo1•Polδ replicates both the leading and lagging DNA strands•Polε does not replicate the leading strand
The current model of eukaryotic DNA replication suggests that DNA polymerase (Pol)ε primarily replicates the leading strand while Polδ replicates the lagging strand. Johnson et al. provide genetic evidence that Polδ replicates both strands, while Polε’s proofreading activity is important for removing Polδ-generated errors from the leading strand.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26145172</pmid><doi>10.1016/j.molcel.2015.05.038</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Substitution Base Pair Mismatch DNA Polymerase II - genetics DNA Polymerase II - metabolism DNA Polymerase III - genetics DNA Polymerase III - metabolism DNA Replication DNA, Fungal - genetics DNA, Fungal - metabolism Exodeoxyribonucleases - genetics Exodeoxyribonucleases - metabolism Genome, Fungal Mutagenesis, Site-Directed Mutation Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism |
title | A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands |
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