AI Article Synopsis
- FANCM is essential for the FANC-BRCA DNA damage response and repair pathway, and the study identifies two associated proteins, MHF1 and MHF2.
- Suppressing MHF1 leads to destabilization of FANCM, impairment in the DNA repair process, and increased chromosome damage from certain drugs.
- The MHF1-MHF2 dimer plays a crucial role in enhancing FANCM's activity and supporting genome maintenance during DNA repair.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848122 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2010.01.036 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!