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

Hishida, T, Kubota, Y, Carr, Antony M and Iwasaki, H (2009) RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light. Nature, 457 (7229). pp. 612-615. ISSN 0028-0836

[img]
Preview
PDF
Download (1MB) | Preview

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(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.

Item Type: Article
Additional Information: Endnotes GDSC276 Nature Publishing Group 10.1038/nature07580
Keywords: DNA-DAMAGE TOLERANCE; NUCLEOTIDE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE; POSTREPLICATION REPAIR; BUDDING YEAST; REPLICATION; CHECKPOINT; PROTEIN; MECHANISMS; UBIQUITIN
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
R Medicine > R Medicine (General)
Depositing User: Gee Wheatley
Date Deposited: 26 Feb 2009
Last Modified: 12 Mar 2017 13:45
URI: http://sro.sussex.ac.uk/id/eprint/2127
Google Scholar:17 Citations

View download statistics for this item

📧 Request an update