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A defect in homologous recombination leads to increased translesion synthesis in E. coli

DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that a...

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Autores principales: Naiman, Karel, Pagès, Vincent, Fuchs, Robert P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027485/
https://www.ncbi.nlm.nih.gov/pubmed/27257075
http://dx.doi.org/10.1093/nar/gkw488
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author Naiman, Karel
Pagès, Vincent
Fuchs, Robert P.
author_facet Naiman, Karel
Pagès, Vincent
Fuchs, Robert P.
author_sort Naiman, Karel
collection PubMed
description DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination.
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spelling pubmed-50274852016-09-21 A defect in homologous recombination leads to increased translesion synthesis in E. coli Naiman, Karel Pagès, Vincent Fuchs, Robert P. Nucleic Acids Res Genome Integrity, Repair and Replication DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. Oxford University Press 2016-09-19 2016-06-01 /pmc/articles/PMC5027485/ /pubmed/27257075 http://dx.doi.org/10.1093/nar/gkw488 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Naiman, Karel
Pagès, Vincent
Fuchs, Robert P.
A defect in homologous recombination leads to increased translesion synthesis in E. coli
title A defect in homologous recombination leads to increased translesion synthesis in E. coli
title_full A defect in homologous recombination leads to increased translesion synthesis in E. coli
title_fullStr A defect in homologous recombination leads to increased translesion synthesis in E. coli
title_full_unstemmed A defect in homologous recombination leads to increased translesion synthesis in E. coli
title_short A defect in homologous recombination leads to increased translesion synthesis in E. coli
title_sort defect in homologous recombination leads to increased translesion synthesis in e. coli
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027485/
https://www.ncbi.nlm.nih.gov/pubmed/27257075
http://dx.doi.org/10.1093/nar/gkw488
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