Rad6–rad18–rad5-pathway-dependent tolerance to chronic low-dose ultraviolet light

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) pathway3,4 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_Δ cells

and demonstrated that Rad52-mediated homologous recombination is required for the viability of the _rad18_Δ 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

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  Download references ACKNOWLEDGEMENTS We thank R. Rothstein and H. Araki for strains; T. Matsunaga for anti-thymine dimer monoclonal antibody (designated TDM2 antibody); and T. Ohya for

technical assistance. This work was supported by the Sumitomo foundation, by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of

Japan, and by the MRC (UK) grant G0600233. AUTHOR CONTRIBUTIONS T.H. designed the study. T.H. and Y.K. performed the experiments. H.I. coordinated the study. T.H., H.I. and A.M.C. analysed

data and wrote the paper. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan , Takashi

Hishida & Yoshino Kubota * MRC Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK Antony M. Carr * International Graduate School of Arts and Sciences,

Yokohama City University, 1-7-29, Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan , Hiroshi Iwasaki Authors * Takashi Hishida View author publications You can also search for this

author inPubMed Google Scholar * Yoshino Kubota View author publications You can also search for this author inPubMed Google Scholar * Antony M. Carr View author publications You can also

search for this author inPubMed Google Scholar * Hiroshi Iwasaki View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to

Takashi Hishida. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary Tables 1-3, Supplementary References and Supplementary Figures 1-10 with Legends. (PDF

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ABOUT THIS ARTICLE CITE THIS ARTICLE Hishida, T., Kubota, Y., Carr, A. _et al._ _RAD6_–_RAD18_–_RAD5_-pathway-dependent tolerance to chronic low-dose ultraviolet light. _Nature_ 457, 612–615

(2009). https://doi.org/10.1038/nature07580 Download citation * Received: 26 March 2008 * Accepted: 24 October 2008 * Published: 14 December 2008 * Issue Date: 29 January 2009 * DOI:

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