InterPro domain: IPR039686

This entry includes a group of evolutionarily conserved ATP-dependent DNA helicases/translocases including human FANCM (Fanconi anemia group M protein) and its homologues, such as Mph1 from S. cerevisiae and Fml1/2 from S. pombe.

FANCM is part of the FA complex that repair the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination [ 1 ]. It also plays a critical role in the replication stress response [ 2 ].

Mph1 can unwind Rad51 D-loops and extended D-loops [ 3 ]. It has been shown to be regulated by the Smc5/6 complex [ 4 , 5 ].

Fml1 promotes Rad51-dependent gene conversion at stalled/blocked replication forks and limits crossing over during mitotic double-strand break repair [ 6 , 7 ].

1. DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun. Signal 15, 41
2. FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres. Proc. Natl. Acad. Sci. U.S.A. 114, E5940-E5949
3. MTE1 Functions with MPH1 in Double-Strand Break Repair. Genetics 203, 147-57
4. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc. Natl. Acad. Sci. U.S.A. 106, 21252-7
5. The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage. PLoS Genet. 13, e1007136
6. The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair. Mol. Cell 32, 118-28
7. The ATPase activity of Fml1 is essential for its roles in homologous recombination and DNA repair. Nucleic Acids Res. 40, 9584-95