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

Shay Covo*, Wenjian Ma, James W. Westmoreland, Dmitry A. Gordenin, Michael A. Resnick

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

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 G2by 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.

Original languageAmerican English
Pages (from-to)3937-3944
Number of pages8
JournalCell Cycle
Volume11
Issue number21
DOIs
StatePublished - 1 Nov 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Drs. Steve Roberts and Kin Chan for critically evaluating this manuscript. This work was supported by the Intramural Research Program of the NIEHS (NIH, DHHS) under project 1Z01ES065073 to M.A.R.

Keywords

  • Cohesin
  • Double-strand breaks
  • Recombination
  • UV

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