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

Mol Cell. 2007 Jul 20;27(2):311-23. doi: 10.1016/j.molcel.2007.06.014.

Abstract

Impaired gap filling and sealing of chromosomal DNA in nucleotide excision repair (NER) leads to genome instability. XRCC1-DNA ligase IIIalpha (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cells, Cultured
  • DNA Breaks, Single-Stranded*
  • DNA Ligase ATP
  • DNA Ligases / chemistry
  • DNA Ligases / metabolism*
  • DNA Polymerase II / chemistry
  • DNA Polymerase II / metabolism
  • DNA Polymerase III / chemistry
  • DNA Polymerase III / metabolism
  • DNA Repair / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Humans
  • Models, Biological
  • Multiprotein Complexes
  • Photobiology
  • Poly-ADP-Ribose Binding Proteins
  • Ultraviolet Rays / adverse effects
  • X-ray Repair Cross Complementing Protein 1
  • Xenopus Proteins

Substances

  • DNA-Binding Proteins
  • LIG1 protein, human
  • Multiprotein Complexes
  • Poly-ADP-Ribose Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Xenopus Proteins
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA Ligases
  • DNA Ligase ATP
  • DNA ligase III alpha protein, Xenopus
  • LIG3 protein, human