Recombination between homologous chromosomes induced by unrepaired UV-generated DNA damage requires Mus81p and is suppressed by Mms2p

PLoS Genet. 2015 Mar 4;11(3):e1005026. doi: 10.1371/journal.pgen.1005026. eCollection 2015 Mar.

Abstract

DNA lesions caused by UV radiation are highly recombinogenic. In wild-type cells, the recombinogenic effect of UV partially reflects the processing of UV-induced pyrimidine dimers into DNA gaps or breaks by the enzymes of the nucleotide excision repair (NER) pathway. In this study, we show that unprocessed pyrimidine dimers also potently induce recombination between homologs. In NER-deficient rad14 diploid strains, we demonstrate that unexcised pyrimidine dimers stimulate crossovers, noncrossovers, and break-induced replication events. The same dose of UV is about six-fold more recombinogenic in a repair-deficient strain than in a repair-proficient strain. We also examined the roles of several genes involved in the processing of UV-induced damage in NER-deficient cells. We found that the resolvase Mus81p is required for most of the UV-induced inter-homolog recombination events. This requirement likely reflects the Mus81p-associated cleavage of dimer-blocked replication forks. The error-free post-replication repair pathway mediated by Mms2p suppresses dimer-induced recombination between homologs, possibly by channeling replication-blocking lesions into recombination between sister chromatids.

Publication types

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

MeSH terms

  • DNA Damage / radiation effects
  • DNA-Binding Proteins / metabolism
  • Endonucleases / metabolism
  • Holliday Junction Resolvases / metabolism
  • Loss of Heterozygosity
  • Pyridines / metabolism
  • Recombination, Genetic
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / radiation effects
  • Saccharomyces cerevisiae Proteins / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ultraviolet Rays

Substances

  • DNA-Binding Proteins
  • MMS2 protein, S cerevisiae
  • Pyridines
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligases
  • Endonucleases
  • MUS81 protein, S cerevisiae
  • Holliday Junction Resolvases
  • Yen1 protein, S cerevisiae
  • pyridine