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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

207 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-323
Number of pages13
JournalMolecular Cell
Volume27
Issue number2
DOIs
Publication statusPublished - 20-Jul-2007

Keywords

  • STRAND BREAK REPAIR
  • UV-INDUCED DAMAGE
  • IN-VIVO
  • MAMMALIAN-CELLS
  • GENE-EXPRESSION
  • MUTANT-CELLS
  • BRCT DOMAIN
  • REPLICATION
  • INHIBITORS
  • DEFECT

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