• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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

Authors

  • Singh TR
  • Saro D
  • Ali AM
  • Zheng XF
  • Du CH
  • Killen MW
  • Sachpatzidis A
  • Wahengbam K
  • Pierce AJ
  • Xiong Y
  • Sung P
  • Meetei AR

Journal

Molecular cell

Publication Data

March 26, 2010

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

Mesh Terms

  • Cell Line, Tumor
  • DNA
  • DNA Helicases
  • DNA-Binding Proteins
  • Fanconi Anemia
  • Histones
  • Humans
  • Protein Binding
  • Protein Folding
  • Protein Multimerization