Authors: Shay Covo, Wenjian Ma, James W. Westmoreland, Dmitry A. Gordenin and Michael A. Resnick

Shay Covo

Corresponding author: covos@niehs.nih.gov
Chromosome Stability Section; Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); Research Triangle Park, NC USA

Wenjian Ma

Chromosome Stability Section; Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); Research Triangle Park, NC USA

James W. Westmoreland

Chromosome Stability Section; Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); Research Triangle Park, NC USA

Dmitry A. Gordenin

Chromosome Stability Section; Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); Research Triangle Park, NC USA
These authors contributed equally to this work.

Michael A. Resnick

Chromosome Stability Section; Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); Research Triangle Park, NC USA
These authors contributed equally to this work.

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.

Received: July 25, 2012; Accepted: August 23, 2012; Published Online: September 17, 2012

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