XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4

Daisy Klein Douwel, Rick A C M Boonen, David T Long, Anna A Szypowska, Markus Räschle, Johannes C Walter, Puck Knipscheer

Research output: Contribution to journal/periodicalArticleScientificpeer-review

237 Citations (Scopus)

Abstract

DNA interstrand crosslinks (ICLs), highly toxic lesions that covalently link the Watson and Crick strands of the double helix, are repaired by a complex, replication-coupled pathway in higher eukaryotes. The earliest DNA processing event in ICL repair is the incision of parental DNA on either side of the ICL ("unhooking"), which allows lesion bypass. Incisions depend critically on the Fanconi anemia pathway, whose activation involves ubiquitylation of the FANCD2 protein. Using Xenopus egg extracts, which support replication-coupled ICL repair, we show that the 3' flap endonuclease XPF-ERCC1 cooperates with SLX4/FANCP to carry out the unhooking incisions. Efficient recruitment of XPF-ERCC1 and SLX4 to the ICL depends on FANCD2 and its ubiquitylation. These data help define the molecular mechanism by which the Fanconi anemia pathway promotes a key event in replication-coupled ICL repair.

Original languageEnglish
Pages (from-to)460-71
Number of pages12
JournalMolecular Cell
Volume54
Issue number3
DOIs
Publication statusPublished - 08 May 2014

Keywords

  • Animals
  • Cell Line
  • Cells, Cultured
  • DNA Cleavage
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Endonucleases
  • Exodeoxyribonucleases
  • Fanconi Anemia Complementation Group D2 Protein
  • Humans
  • Kinetics
  • Protein Binding
  • Recombinases
  • Ubiquitination
  • Xenopus Proteins
  • Xenopus laevis

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