Singh, T. R. et al. MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM. Mol. Cell 37, 879-886

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Molecular cell (Impact Factor: 14.46). 03/2010; 37(6):879-86. DOI: 10.1016/j.molcel.2010.01.036
Source: PubMed

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.

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Available from: Xiao-Feng Zheng, Aug 26, 2015
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    • "In higher eukaryotes, multiple DNA repair pathways are also involved in the resolution of ICLs, albeit the existence of the specialized Fanconi anemia (FA) pathway [9] marks a significant difference compared to the yeasts. The current model for the involvement of the FA pathway in ICL repair is as follows: the ICL is recognized by FANCM-FAAP24 bound to the recently discovered MHF complex [9] [10] [11]. FANCM-FAAP24-MHF recruits a downstream E3 ubiquitin ligase complex known as the " FA core complex " , which in turn monoubiquitinates FANCD2 and FANCI on chromatin [9] [12]. "
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