This entry represents the pseudonuclease domain (PND) from the FANCM protein []. This domain is part of the PD(D/E)XK superfamily but does not appear to have a full set of catalytic residues [].
This entry represents a structured region found in the Fanconi anemia group M protein (FANCM) that binds to a two-histone-fold-containing protein complex MHF. MHF binds double-strand DNA, stimulates the DNA-binding activity of FANCM, and contributes to the targeting of FANCM to chromatin [].
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 []. It also plays a critical role in the replication stress response []. Mph1 can unwind Rad51 D-loops and extended D-loops []. It has been shown to be regulated by the Smc5/6 complex [, ]. Fml1 promotes Rad51-dependent gene conversion at stalled/blocked replication forks and limits crossing over during mitotic double-strand break repair [, ].
Centromere protein X (CENP-X) is a component of several different complexes, including the multisubunit FA complex, the heterotetrameric CENP-T-W-S-X complex and the APITD1/CENPS complex. The Fanconi anemia (FA) core complex is involved in DNA damage repair and genome maintenance. The FA complex is composed of CENPS, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM, FAAP24 and CENPX. Interacts with CENPS, FANCM and FAAP24 [, ]. Inner kinetochore subunit mhf2 is the dsDNA-binding component of the FANCM-MHF complex, important for gene conversion at blocked replication forks []and non-crossover recombination during mitosis and meiosis [].The CENP-T-W-S-X complex binds, supercoils DNA and plays an important role in kinetochore assembly [].The APITD1/CENPS complex is composed of at least of CENP-S and CENP-X and is essential for the stable assembly of the outer kinetchore [].
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 []. 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 []. 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 []. In vitro, on its own, it strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA []. FANCM is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding [, ].
