RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light

Nature. 2009 Jan 29;457(7229):612-5. doi: 10.1038/nature07580. Epub 2008 Dec 14.

Abstract

In nature, organisms are exposed to chronic low-dose ultraviolet light (CLUV) as opposed to the acute high doses common to laboratory experiments. Analysis of the cellular response to acute high-dose exposure has delineated the importance of direct DNA repair by the nucleotide excision repair pathway and for checkpoint-induced cell cycle arrest in promoting cell survival. Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error-free postreplication repair (RAD6 error-free PRR) pathway in promoting cell growth and survival. We show that loss of the RAD6 error-free PRR pathway results in DNA-damage-checkpoint-induced G2 arrest in CLUV-exposed cells, whereas wild-type and nucleotide-excision-repair-deficient cells are largely unaffected. Cell cycle arrest in the absence of the RAD6 error-free PRR pathway was not caused by a repair defect or by the accumulation of ultraviolet-induced photoproducts. Notably, we observed increased replication protein A (RPA)- and Rad52-yellow fluorescent protein foci in the CLUV-exposed rad18Delta cells and demonstrated that Rad52-mediated homologous recombination is required for the viability of the rad18Delta cells after release from CLUV-induced G2 arrest. These and other data presented suggest that, in response to environmental levels of ultraviolet exposure, the RAD6 error-free PRR pathway promotes replication of damaged templates without the generation of extensive single-stranded DNA regions. Thus, the error-free PRR pathway is specifically important during chronic low-dose ultraviolet exposure to prevent counter-productive DNA checkpoint activation and allow cells to proliferate normally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / deficiency
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • DNA Damage
  • DNA Helicases
  • DNA Repair / radiation effects*
  • DNA Replication / radiation effects
  • DNA, Fungal / radiation effects
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • G2 Phase / radiation effects
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Recombination, Genetic
  • Replication Protein A / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / radiation effects*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Conjugating Enzymes / deficiency
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Ultraviolet Rays*

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • RAD18 protein, S cerevisiae
  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • RAD6 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • Adenosine Triphosphatases
  • RAD5 protein, S cerevisiae
  • DNA Helicases