1. Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
2. MRC Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK
3. International Graduate School of Arts and Sciences, Yokohama City University, 1-7-29, Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan

Correspondence to: Takashi Hishida¹ Correspondence and requests for materials should be addressed to T.H. (Email: hishida@biken.osaka-u.ac.jp).

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 pathway¹ and for checkpoint-induced cell cycle arrest in promoting cell survival². 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^{3, 4} 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 foci⁵ in the CLUV-exposed rad18 cells and demonstrated that Rad52-mediated homologous recombination is required for the viability of the rad18 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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.