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

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.
Authors	Daisy Klein Douwel, Rick A C M Boonen, David T Long, Anna A Szypowska, Markus Räschle, Johannes C Walter, Puck Knipscheer
Journal	Molecular cell (Mol Cell) Vol. 54 Issue 3 Pg. 460-71 (May 08 2014) ISSN: 1097-4164 [Electronic] United States
PMID	24726325 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2014 Elsevier Inc. All rights reserved.
Chemical References	DNA-Binding Proteins FANCD2 protein, human Fanconi Anemia Complementation Group D2 Protein Multifunctional Enzymes Recombinases Xenopus Proteins xeroderma pigmentosum group F protein ERCC1 protein, human Endodeoxyribonucleases Endonucleases Exodeoxyribonucleases FAN1 protein, human MUS81 protein, human SLX4 protein, human
Topics	Animals Cell Line Cells, Cultured DNA Cleavage DNA Damage DNA Repair DNA-Binding Proteins (chemistry, metabolism) Endodeoxyribonucleases Endonucleases (chemistry, metabolism) Exodeoxyribonucleases (metabolism) Fanconi Anemia Complementation Group D2 Protein (chemistry, metabolism) Humans Kinetics Multifunctional Enzymes Protein Binding Recombinases (chemistry, metabolism) Ubiquitination Xenopus Proteins (chemistry, metabolism) Xenopus laevis

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