Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2012-11, Vol.11 (21), p.3937-3944
• Main Authors: Covo, Shay, Ma, Wenjian, Westmoreland, James W., Gordenin, Dmitry A., Resnick, Michael A.
• Format: Article
• Language: English
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Cycle Proteins - metabolism; Chromatids - metabolism; Chromosomal Proteins, Non-Histone - metabolism; cohesin; Cohesins; Cycle; DNA Breaks, Double-Stranded; double-strand breaks; G1 Phase; G2 Phase; Humans; Landes; Loss of Heterozygosity; Organogenesis; Proteins; Radiation, Ionizing; recombination; Recombination, Genetic; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - radiation effects; Ultraviolet Rays
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.21945

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 G 1 through processing of closely spaced single-strand lesions to DSBs. However, other scenarios are possible, since the recombination initiated in G 1 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 G 2 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 G 2 . 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.