InterPro domain: IPR044749

This entry represents the N-terminal domain of FANCM. It contains the ATP-binding region.

Fanconi anemia group M (FANCM) protein is a DNA-dependent ATPase component of the Fanconi anemia (FA) core complex [ 1 ]. It is required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage [ 2 ]. In complex with CENPS and CENPX, it binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA), and Holliday junction substrates. Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX. In complex with FAAP24, it efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates [ 3 ]. In vitro, on its own, it strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA [ 4 ]. FANCM is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding [ 5 , 6 ].

1. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet 37, 174-80
2. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood 114
3. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol. Cell 25, 505-16
4. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol. Cell 37, 865-78
5. From unwinding to clamping - the DEAD box RNA helicase family. Nat. Rev. Mol. Cell Biol. 12, 958-63
6. Comparative structural analysis of human DEAD-box RNA helicases. PLoS ONE 5, 331-43