RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light.
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.
Hishida
Takashi
T
Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. hishida@biken.osaka-u.ac.jp
Kubota
Yoshino
Y
Carr
Antony M
AM
Iwasaki
Hiroshi
H
D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair / Q000528:radiation effects*; D004261:DNA Replication / Q000528:radiation effects; D004271:DNA, Fungal / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase / Q000528:radiation effects; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D011995:Recombination, Genetic; D051716:Replication Protein A / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C063607:RAD18 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases