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MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM.

Molecular cell | Mar 26, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20347429

FANCM is a Fanconi anemia nuclear core complex protein required for the functional integrity of the FANC-BRCA pathway of DNA damage response and repair. Here we report the isolation and characterization of two histone-fold-containing FANCM-associated proteins, MHF1 and MHF2. We show that suppression of MHF1 expression results in (1) destabilization of FANCM and MHF2, (2) impairment of DNA damage-induced monoubiquitination and foci formation of FANCD2, (3) defective chromatin localization of FA nuclear core complex proteins, (4) elevated MMC-induced chromosome aberrations, and (5) sensitivity to MMC and camptothecin. We also provide biochemical evidence that MHF1 and MHF2 assemble into a heterodimer that binds DNA and enhances the DNA branch migration activity of FANCM. These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM.

Pubmed ID: 20347429 RIS Download

Mesh terms: Cell Line, Tumor | DNA | DNA Helicases | DNA-Binding Proteins | Fanconi Anemia | Histones | Humans | Protein Binding | Protein Folding | Protein Multimerization

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Associated grants

  • Agency: NIEHS NIH HHS, Id: ES015632
  • Agency: NIEHS NIH HHS, Id: ES07061
  • Agency: NHLBI NIH HHS, Id: HL084082
  • Agency: NHLBI NIH HHS, Id: R01 HL084082
  • Agency: NHLBI NIH HHS, Id: R01 HL084082-02

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