title: A defect in homologous recombination leads to increased translesion synthesis in E. coli.
abstract: 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.
authors.affiliation: Team DNA Damage Tolerance, Cancer Research Center of Marseille (CRCM), CNRS, UMR7258, Marseille, F-13009, France Inserm, U1068, CRCM, Marseille, F-13009, France Institut Paoli-Calmettes, Marseille, F-13009, France Aix-Marseille University, UM 105, F-13284, Marseille, France.
authors.forename: Karel
authors.initials: K
authors.lastname: Naiman
authors.affiliation: Team DNA Damage Tolerance, Cancer Research Center of Marseille (CRCM), CNRS, UMR7258, Marseille, F-13009, France Inserm, U1068, CRCM, Marseille, F-13009, France Institut Paoli-Calmettes, Marseille, F-13009, France Aix-Marseille University, UM 105, F-13284, Marseille, France vincent.pages@inserm.fr.
authors.forename: Vincent
authors.identifier: 0000-0002-3059-2903
authors.initials: V
authors.lastname: Pagès
authors.affiliation: Team DNA Damage Tolerance, Cancer Research Center of Marseille (CRCM), CNRS, UMR7258, Marseille, F-13009, France Inserm, U1068, CRCM, Marseille, F-13009, France Institut Paoli-Calmettes, Marseille, F-13009, France Aix-Marseille University, UM 105, F-13284, Marseille, France robert.fuchs@inserm.fr.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Fuchs
mesh_terms: D000483:Alleles; D004249:DNA Damage; D004269:DNA, Bacterial / Q000096:biosynthesis*; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics*; D013014:SOS Response, Genetics / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins