Fanconi anemia group M protein (FANCM)

Fanconi anemia group M protein (FANCM) is a multifunctional DNA repair factor central to the Fanconi anemia (FA) network, safeguarding genomic integrity by orchestrating a variety of DNA damage repair and checkpoint processes[2][3][5]. FANCM acts as an ATP-dependent DNA translocase and is critical for recognizing and remodeling aberrant DNA structures, such as Holliday junctions and stalled replication forks, promoting branch migration and fork restart while suppressing deleterious recombination[2][3][6]. As a key scaffold in the FA core complex, FANCM anchors accessory proteins such as FAAP24, MHF1, and MHF2 to chromatin, facilitating the monoubiquitination of FANCI and FANCD2—an essential step in DNA interstrand crosslink repair[5][7]. FANCM deficiency or mutation impairs these processes, leading to Fanconi anemia, marked by chromosomal instability, bone marrow failure, developmental defects, and increased risk for various cancers[1][3][5]. Although there are no drugs that directly target FANCM, its activity modulates sensitivity to DNA crosslinking agents used in chemotherapy[5].

Other names

Fanconi anemia group M proteinFANCMKIAA1596Protein FACMFAAP250ATP-dependent RNA helicase FANCMFanconi anemia-associated polypeptide of 250 kDaProtein Hef orthologPOF15SPGF28

Indirect, through modulation of cellular response to DNA crosslinking agents and replication stress[5] Loss or inhibition of FANCM disables DNA repair, increasing cytotoxicity of DNA crosslinking drugs[5]