Interstrand crosslink repair: can XPF-ERCC1 be let off the hook?

Trends Genet. 2008 Feb;24(2):70-6. doi: 10.1016/j.tig.2007.11.003. Epub 2008 Jan 14.

Abstract

The interstrand crosslink (ICL) presents a challenge to both the cell and the scientist. From a clinical standpoint, these lesions are particularly intriguing: ICL-inducing agents are powerful tools in cancer chemotherapy, and spontaneous ICLs have recently been linked with accelerated aging phenotypes. Nevertheless, the ICL repair process has proven difficult to elucidate. Here we discuss recent additions to the current model and argue that the endonuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1 (XPF-ERCC1) has been heretofore misplaced. During nucleotide excision repair, XPF-ERCC1 makes a single-strand nick adjacent to the lesion. XPF-ERCC1 has been thought to play an analogous role in ICL repair. However, recent data has implicated XPF-ERCC1 in homologous recombination. We suggest that this role, rather than its function in nucleotide excision repair, defines its importance to ICL repair.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Genetic Complementation Test
  • Humans
  • Models, Biological
  • Recombination, Genetic
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / metabolism

Substances

  • DNA-Binding Proteins
  • xeroderma pigmentosum group F protein
  • ERCC1 protein, human
  • Endonucleases