Abstract
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 ~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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Binding Sites
-
Crystallography, X-Ray
-
DNA / chemistry
-
DNA / metabolism
-
DNA Repair*
-
DNA, Single-Stranded / chemistry
-
DNA, Single-Stranded / metabolism
-
Fanconi Anemia / genetics
-
Fanconi Anemia Complementation Group D2 Protein / chemistry*
-
Fanconi Anemia Complementation Group D2 Protein / metabolism
-
Fanconi Anemia Complementation Group Proteins / chemistry*
-
Fanconi Anemia Complementation Group Proteins / metabolism
-
Hydrophobic and Hydrophilic Interactions
-
Mice
-
Models, Molecular
-
Molecular Sequence Data
-
Phosphorylation
-
Protein Binding
-
Protein Conformation
-
Protein Folding
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Static Electricity
-
Ubiquitin / chemistry
-
Ubiquitination
Substances
-
DNA, Single-Stranded
-
FANCI protein, mouse
-
Fancd2 protein, mouse
-
Fanconi Anemia Complementation Group D2 Protein
-
Fanconi Anemia Complementation Group Proteins
-
Ubiquitin
-
DNA
Associated data
-
PDB/3S4W
-
PDB/3S4Z
-
PDB/3S51