title: Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation.
abstract: 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.affiliation: Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sertic
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzi
authors.forename: Ross
authors.initials: R
authors.lastname: Cloney
authors.forename: Alan R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: Federica
authors.initials: F
authors.lastname: Marini
authors.forename: Paolo
authors.initials: P
authors.lastname: Plevani
authors.forename: Marco
authors.initials: M
authors.lastname: Muzi-Falconi
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D054875:Ubiquitination; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes