RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network.

Abstract	The Fanconi anemia (FA) network is important for the repair of interstrand DNA cross-links. A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase. In this study, we show that RAD18, another DNA damage-activated E3 ubiquitin ligase, also participates in ID complex activation by ubiquitylating proliferating cell nuclear antigen (PCNA) on Lys164, an event required for the recruitment of FANCL to chromatin. We also found that monoubiquitylated PCNA stimulates FANCL-catalyzed FANCD2 and FANCI monoubiquitylation. Collectively, these experiments identify RAD18-mediated PCNA monoubiquitination as a central hub for the mobilization of the FA pathway by promoting FANCL-mediated FANCD2 monoubiquitylation.
Authors	Liyi Geng, Catherine J Huntoon, Larry M Karnitz
Journal	The Journal of cell biology (J Cell Biol) Vol. 191 Issue 2 Pg. 249-57 (Oct 18 2010) ISSN: 1540-8140 [Electronic] United States
PMID	20937699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Chromatin Cross-Linking Reagents DNA-Binding Proteins FANCD2 protein, human Fanconi Anemia Complementation Group D2 Protein Proliferating Cell Nuclear Antigen RAD18 protein, human FANCL protein, human Fanconi Anemia Complementation Group L Protein Ubiquitin-Protein Ligases Cisplatin
Topics	Binding Sites Chromatin (metabolism) Cisplatin (pharmacology) Cross-Linking Reagents (pharmacology) DNA Repair DNA-Binding Proteins (genetics, metabolism, physiology) Fanconi Anemia Complementation Group D2 Protein (genetics, metabolism, physiology) Fanconi Anemia Complementation Group L Protein (chemistry, metabolism, physiology) HeLa Cells Humans Models, Genetic Proliferating Cell Nuclear Antigen (chemistry, metabolism) Protein Structure, Tertiary RNA Interference Ubiquitin-Protein Ligases Ubiquitination

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