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PMID: 22266823 Published · epublish English Journal Article Research Support, N.I.H., Extramural

Regulation of Rev1 by the Fanconi anemia core complex.

Nature structural & molecular biology ·Vol. 19 ·No. 2 ·2012-01-22 ·Pages 164-70

Kim H, Yang K, Dejsuphong D, D'Andrea AD

Abstract

The 15 known Fanconi anemia proteins cooperate in a pathway that regulates DNA interstrand cross-link repair. Recent studies indicate that the Fanconi anemia pathway also controls Rev1-mediated translesion DNA synthesis (TLS). We identified Fanconi anemia-associated protein (FAAP20), an integral subunit of the multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is required for stability of the complex and monoubiquitination of FANCD2. FAAP20 contains a ubiquitin-binding zinc finger 4 domain and binds to the monoubiquitinated form of Rev1. FAAP20 binding stabilizes Rev1 nuclear foci and promotes interaction of the Fanconi anemia core with PCNA-Rev1 DNA damage bypass complexes. FAAP20 therefore provides a critical link between the Fanconi anemia pathway and TLS polymerase activity. We propose that the Fanconi anemia core complex regulates cross-link repair by channeling lesions to damage bypass pathways and preventing large DNA insertions and deletions.

MeSH Terms
Fanconi Anemia Complementation Group Proteins/metabolism Gene Expression Regulation Nuclear Proteins/metabolism Nucleotidyltransferases/metabolism Protein Binding Protein Stability
Chemicals
FAAP20 protein, human Fanconi Anemia Complementation Group Proteins Nuclear Proteins Nucleotidyltransferases REV1 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kim Hyungjin
Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Yang Kailin
Dejsuphong Donniphat
D'Andrea Alan D
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2222
Published
2012-01-22
Epub
2012-00-22
Pages
164-70
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3280818
Subset
IM
Grants
NHLBI NIH HHS · R37 HL052725-19 · United States
NHLBI NIH HHS · R37 HL052725 · United States
NHLBI NIH HHS · R01 HL052725 · United States
NIDDK NIH HHS · R01 DK043889-20 · United States
NHLBI NIH HHS · R01HL52725 · United States
NIDDK NIH HHS · R01 DK043889 · United States
NIDDK NIH HHS · R01DK43889 · United States
External Links
PubMed source DOI: 10.1038/nsmb.2222 PMC Full Text View journal details
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