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Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation
journal contribution
posted on 2023-06-07, 23:20 authored by Sarah Sertic, Sara Pizzi, Ross Cloney, Alan LehmannAlan Lehmann, Federica Marini, Paolo Plevani, Marco Muzi-FalconiUV 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.
History
Publication status
- Published
Journal
Proceedings of the National Academy of SciencesISSN
1091-6490Publisher
National Academy of SciencesPublisher URL
External DOI
Issue
33Volume
108Page range
13647-13652Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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