Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner

Jill Moser, Hanneke Kool, Ioannis Giakzidis, Keith Caldecott, Leon H. F. Mullenders*, Maria I. Fousteri

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

208 Citaten (Scopus)


Impaired gap filling and sealing of chromosomal DNA in nucleotide excision repair (NER) leads to genome instability. XRCC1-DNA ligase III alpha (XRCC1-Lig3) plays a central role in the repair of DNA single-strand breaks but has never been implicated in NER. Here we show that XRCC1-Lig3 is indispensable for ligation of NER-induced breaks and repair of UV lesions in quiescent cells. Furthermore, our results demonstrate that two distinct complexes differentially carry out gap filling in NER. XRCC1-Lig3 and DNA polymerase delta colocalize and interact with NER components in a UV- and incision-dependent manner throughout the cell cycle. In contrast, DNA ligase I and DNA polymerase epsilon are recruited to UV-damage sites only in proliferating cells. This study reveals an unexpected and key role for XRCC1-Lig3 in maintenance of genomic integrity by NER in both dividing and nondividing cells and provides evidence for cell-cycle regulation of NER-mediated repair synthesis in vivo.

Originele taal-2English
Pagina's (van-tot)311-323
Aantal pagina's13
TijdschriftMolecular Cell
Nummer van het tijdschrift2
StatusPublished - 20-jul-2007

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