title: Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion.
abstract: Ultraviolet light (UV) can provoke genome instability, partly through its ability to induce homologous recombination (HR). However, the mechanism(s) of UV-induced recombination is poorly understood. Although double-strand breaks (DSBs) have been invoked, there is little evidence for their generation by UV. Alternatively, single-strand DNA lesions that stall replication forks could provoke recombination. Recent findings suggest efficient initiation of UV-induced recombination in G1 through processing of closely spaced single-strand lesions to DSBs. However, other scenarios are possible, since the recombination initiated in G1 can be completed in the following stages of the cell cycle. We developed a system that could address UV-induced recombination events that start and finish in G2 by manipulating the activity of the sister chromatid cohesion complex. Here we show that sister-chromatid cohesion suppresses UV-induced recombination events that are initiated and resolved in G2. By comparing recombination frequencies and survival between UV and ionizing radiation, we conclude that a substantial portion of UV-induced recombination occurs through DSBs. This notion is supported by a direct physical observation of UV-induced DSBs that are dependent on nucleotide excision repair. However, a significant role of nonDSB intermediates in UV-induced recombination cannot be excluded.
authors.affiliation: Chromosome Stability Section, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, USA. covos@niehs.nih.gov
authors.forename: Shay
authors.initials: S
authors.lastname: Covo
authors.forename: Wenjian
authors.initials: W
authors.lastname: Ma
authors.forename: James W
authors.initials: JW
authors.lastname: Westmoreland
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Gordenin
authors.forename: Michael A
authors.initials: MA
authors.lastname: Resnick
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D016193:G1 Phase; D016195:G2 Phase; D006801:Humans; D019656:Loss of Heterozygosity; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins