title: FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA.
abstract: Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and -M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Abdullah Mahmood
authors.initials: AM
authors.lastname: Ali
authors.forename: Thiyam Ramsing
authors.initials: TR
authors.lastname: Singh
authors.forename: Amom Ruhikanta
authors.initials: AR
authors.lastname: Meetei
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D055808:Drug Discovery; D005199:Fanconi Anemia / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C518296:FAAP24 protein, human; D051856:Fanconi Anemia Complementation Group Proteins; D004247:DNA; C518295:FANCM protein, human; D004265:DNA Helicases