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Title: Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the {approx}300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.
Authors:
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Publication Date:
OSTI Identifier:
1041968
Report Number(s):
BNL--97646-2012-JA
Journal ID: ISSN 0036-8075; SCIEAS; TRN: US201212%%379
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Science (Washington, D.C.); Journal Volume: 333; Journal Issue: 6040
Research Org:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org:
USDOE SC OFFICE OF SCIENCE (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANEMIAS; CRYSTAL STRUCTURE; DEFECTS; DNA; DNA REPAIR; ELECTRON DENSITY; IN VITRO; NEOPLASMS; PHOSPHORYLATION; PROTEINS; REPAIR