FANCM

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Fanconi Anemia Complementation Group M

DNA-dependent ATPase component of the Fanconi anemia (FA) core complex (PubMed:16116422).

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 (PubMed:16116422, PubMed:19423727, PubMed:20347428, PubMed:20347429, PubMed:29231814).

In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates (PubMed:20347428, PubMed:20347429).

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 (PubMed:20347429).

In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates (PubMed:17289582).

In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA (PubMed:16116434).

Double-strand break repair via synthesis-dependent strand annealing Source: GO_Central
Interstrand cross-link repair Source: GO_Central
Positive regulation of protein monoubiquitination Source: UniProtKB
Replication fork processing Source: UniProtKB
Replication fork reversal Source: GO_Central
Resolution of meiotic recombination intermediates Source: UniProtKB

Nucleus

Spermatogenic failure 28 (SPGF28):
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in oligoasthenospermia or non-obstructive azoospermia.
Premature ovarian failure 15 (POF15):
An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.

Phosphorylated; hyperphosphorylated in response to genotoxic stress.