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

Cell Cycle. 2012 Nov 1;11(21):3937-44. doi: 10.4161/cc.21945. Epub 2012 Sep 17.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cohesins
  • DNA Breaks, Double-Stranded
  • G1 Phase
  • G2 Phase
  • Humans
  • Loss of Heterozygosity
  • Radiation, Ionizing
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / radiation effects
  • Ultraviolet Rays*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone