AI Article Synopsis
- The MHF1-MHF2 (MHF) complex is vital for activating the Fanconi anaemia pathway and managing DNA damage through processes like homologous recombination and replication fork maintenance.
- Recent studies revealed the crystal structure of an MHF-DNA complex, demonstrating that MHF prefers to bind to branched DNA structures rather than regular double-stranded DNA.
- Biochemical and genetic experiments showed that the specific way MHF binds to DNA is essential for helping cells resist DNA damage, highlighting its role in genome maintenance.
Article Abstract
The conserved MHF1-MHF2 (MHF) complex functions in the activation of the Fanconi anaemia pathway of the DNA damage response, in regulating homologous recombination, and in DNA replication fork maintenance. MHF facilitates the processing of multiple types of branched DNAs by the DNA translocase FANCM. Here we report the crystal structure of a human MHF-DNA complex that reveals the DNA-binding mode of MHF. The structure suggests that MHF prefers branched DNA over double-stranded DNA because it engages two duplex arms. Biochemical analyses verify that MHF preferentially engages DNA forks or various four-way junctions independent of the junction-site structure. Furthermore, genetic experiments provide evidence that the observed DNA-binding interface of MHF is important for cellular resistance to DNA damage. These results offer insights into how the MHF complex recognizes branched DNA and stimulates FANCM activity at such a structure to promote genome maintenance.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967914 | PMC |
| http://dx.doi.org/10.1038/ncomms3987 | DOI Listing |
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