Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 33, Pages 13647-13652Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1108547108
Keywords
local UV damage; UV lesion processing; ssDNA; ubiquitin
Categories
Funding
- Associazione Italiana Ricerca sul Cancro and Fondazione Cariplo
- European Union [512113]
- Telethon-Italy [GGP030406]
- EMBO
- Medical Research Council
- Medical Research Council [G0501450, G0801130B] Funding Source: researchfish
- MRC [G0501450] Funding Source: UKRI
Ask authors/readers for more resources
UV light induces DNA lesions, which are removed by nucleotide excision repair (NER). Exonuclease 1 (EXO1) is highly conserved from yeast to human and is implicated in numerous DNA metabolic pathways, including repair, recombination, replication, and telomere maintenance. Here we show that hEXO1 is involved in the cellular response to UV irradiation in human cells. After local UV irradiation, fluorescent-tagged hEXO1 localizes, together with NER factors, at the sites of damage in nonreplicating cells. hEXO1 accumulation requires XPF-dependent processing of UV-induced lesions and is enhanced by inhibition of DNA repair synthesis. In nonreplicating cells, depletion of hEXO1 reduces unscheduled DNA synthesis after UV irradiation, prevents ubiquitylation of histone H2A, and impairs activation of the checkpoint signal transduction cascade in response to UV damage. These findings reveal a key role for hEXO1 in the UV-induced DNA damage response linking NER to checkpoint activation in human cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available