PMID- 20937699 OWN - NLM STAT- MEDLINE DCOM- 20110222 LR - 20230406 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 191 IP - 2 DP - 2010 Oct 18 TI - RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network. PG - 249-57 LID - 10.1083/jcb.201005101 [doi] AB - 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. FAU - Geng, Liyi AU - Geng L AD - Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. FAU - Huntoon, Catherine J AU - Huntoon CJ FAU - Karnitz, Larry M AU - Karnitz LM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101011 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Chromatin) RN - 0 (Cross-Linking Reagents) RN - 0 (DNA-Binding Proteins) RN - 0 (FANCD2 protein, human) RN - 0 (Fanconi Anemia Complementation Group D2 Protein) RN - 0 (Proliferating Cell Nuclear Antigen) RN - 0 (RAD18 protein, human) RN - EC 2.3.2.27 (FANCL protein, human) RN - EC 2.3.2.27 (Fanconi Anemia Complementation Group L Protein) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Binding Sites MH - Chromatin/metabolism MH - Cisplatin/pharmacology MH - Cross-Linking Reagents/pharmacology MH - *DNA Repair MH - DNA-Binding Proteins/genetics/metabolism/*physiology MH - Fanconi Anemia Complementation Group D2 Protein/genetics/metabolism/*physiology MH - Fanconi Anemia Complementation Group L Protein/chemistry/metabolism/physiology MH - HeLa Cells MH - Humans MH - Models, Genetic MH - Proliferating Cell Nuclear Antigen/chemistry/*metabolism MH - Protein Structure, Tertiary MH - RNA Interference MH - Ubiquitin-Protein Ligases MH - Ubiquitination PMC - PMC2958487 EDAT- 2010/10/13 06:00 MHDA- 2011/02/23 06:00 PMCR- 2011/04/18 CRDT- 2010/10/13 06:00 PHST- 2010/10/13 06:00 [entrez] PHST- 2010/10/13 06:00 [pubmed] PHST- 2011/02/23 06:00 [medline] PHST- 2011/04/18 00:00 [pmc-release] AID - jcb.201005101 [pii] AID - 201005101 [pii] AID - 10.1083/jcb.201005101 [doi] PST - ppublish SO - J Cell Biol. 2010 Oct 18;191(2):249-57. doi: 10.1083/jcb.201005101. Epub 2010 Oct 11.