MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM

Thiyam Ramsing Singh, Dorina Saro, Abdullah Mahmood Ali, Xiao Feng Zheng, Chang hu Du, Michael W. Killen, Aristidis Sachpatzidis, Kebola Wahengbam, Andrew J. Pierce, Yong Xiong, Patrick Sung, Amom Ruhikanta Meetei

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)879-886
Number of pages8
JournalMolecular Cell
Volume37
Issue number6
DOIs
StatePublished - Mar 26 2010
Externally publishedYes

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM'. Together they form a unique fingerprint.

  • Cite this

    Singh, T. R., Saro, D., Ali, A. M., Zheng, X. F., Du, C. H., Killen, M. W., Sachpatzidis, A., Wahengbam, K., Pierce, A. J., Xiong, Y., Sung, P., & Meetei, A. R. (2010). MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM. Molecular Cell, 37(6), 879-886. https://doi.org/10.1016/j.molcel.2010.01.036