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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 ~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

Authors

  • Joo W
  • Xu G
  • Persky NS
  • Smogorzewska A
  • Rudge DG
  • Buzovetsky O
  • Elledge SJ
  • Pavletich NP

Journal

Science (New York, N.Y.)

Publication Data

July 15, 2011

Associated Grants

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

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