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

Liyi Geng, Catherine J. Huntoon, Larry M. Karnitz

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalJournal of Cell Biology
Volume191
Issue number2
DOIs
StatePublished - Oct 18 2010

ASJC Scopus subject areas

  • Cell Biology

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