title: A recombination execution checkpoint regulates the choice of homologous recombination pathway during DNA double-strand break repair.
abstract: A DNA double-strand break (DSB) is repaired by gene conversion (GC) if both ends of the DSB share homology with an intact DNA sequence. However, if homology is limited to only one of the DSB ends, repair occurs by break-induced replication (BIR). It is not known how the homology status of the DSB ends is first assessed and what other parameters govern the choice between these repair pathways. Our data suggest that a "recombination execution checkpoint" (REC) regulates the choice of the homologous recombination pathway employed to repair a given DSB. This choice is made prior to the initiation of DNA synthesis, and is dependent on the relative position and orientation of the homologous sequences used for repair. The RecQ family helicase Sgs1 plays a key role in regulating the choice of the recombination pathway. Surprisingly, break repair and gap repair are fundamentally different processes, both kinetically and genetically, as Pol32 is required only for gap repair. We propose that the REC may have evolved to preserve genome integrity by promoting conservative repair, especially when a DSB occurs within a repeated sequence.
authors.affiliation: Department of Biology and Rosenstiel Medical Center, Brandeis University, Waltham, Massachuetts 02454, USA.
authors.forename: Suvi
authors.initials: S
authors.lastname: Jain
authors.forename: Neal
authors.initials: N
authors.lastname: Sugawara
authors.forename: John
authors.initials: J
authors.lastname: Lydeard
authors.forename: Moreshwar
authors.initials: M
authors.lastname: Vaze
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tanguy Le Gac
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology*; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005785:Gene Conversion; D007700:Kinetics; D008954:Models, Biological; D008957:Models, Genetic; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases