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Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway.

Science (New York, N.Y.) | Jul 15, 2011

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.

Pubmed ID: 21764741 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Binding Sites | Crystallography, X-Ray | DNA | DNA Repair | DNA, Single-Stranded | Fanconi Anemia | Fanconi Anemia Complementation Group D2 Protein | Fanconi Anemia Complementation Group Proteins | 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 | Ubiquitination

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM044664
  • Agency: NCI NIH HHS, Id: T32 CA009216-32
  • Agency: NIGMS NIH HHS, Id: R01 GM044664-10
  • Agency: NCI NIH HHS, Id: T32 CA009216
  • Agency: Howard Hughes Medical Institute, Id: R37 GM044664
  • Agency: NIGMS NIH HHS, Id:

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