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

被引:65
作者
Hishida, Takashi [1 ]
Kubota, Yoshino [1 ]
Carr, Antony M. [2 ]
Iwasaki, Hiroshi [3 ]
机构
[1] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan
[2] Univ Sussex, MRC Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England
[3] Yokohama City Univ, Int Grad Sch Arts & Sci, Kanagawa 2300045, Japan
关键词
DNA-DAMAGE TOLERANCE; NUCLEOTIDE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE; POSTREPLICATION REPAIR; BUDDING YEAST; REPLICATION; CHECKPOINT; PROTEIN; MECHANISMS; UBIQUITIN;
D O I
10.1038/nature07580
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1) and for checkpoint-induced cell cycle arrest in promoting cell survival(2). 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 foci(5) in the CLUV- exposed rad18 Delta cells and demonstrated that Rad52- mediated homologous recombination is required for the viability of the rad18 Delta 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.
引用
收藏
页码:612 / U124
页数:5
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