Structural and functional relationships of the XPF/MUS81 family of proteins.
Proteins belonging to the XPF/MUS81 family play important roles in the repair of DNA lesions caused by UV-light or DNA cross-linking agents. Most eukaryotes have four family members that assemble into two distinct heterodimeric complexes, XPF-ERCC1 and MUS81-EME1. Each complex contains one catalytic and one noncatalytic subunit and exhibits endonuclease activity with a variety of 3'-flap or fork DNA structures. The catalytic subunits share a characteristic core containing an excision repair cross complementation group 4 (ERCC4) nuclease domain and a tandem helix-hairpin-helix (HhH)(2) domain. Diverged domains are present in the noncatalytic subunits and may be required for substrate targeting. Vertebrates possess two additional family members, FANCM and Fanconi anemia-associated protein 24 kDa (FAAP24), which possess inactive nuclease domains. Instead, FANCM contains a functional Superfamily 2 (SF2) helicase domain that is required for DNA translocation. Determining how these enzymes recognize specific DNA substrates and promote key repair reactions is an important challenge for the future.
Ciccia
Alberto
A
London Research Institute, Cancer Research UK, Clare Hall Laboratories, Hertfordshire, United Kingdom.
McDonald
Neil
N
West
Stephen C
SC
D000595:Amino Acid Sequence; D000818:Animals; D001671:Biochemistry / Q000379:methods; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004720:Endonucleases / Q000378:metabolism / Q000502:physiology*; D019143:Evolution, Molecular; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008540:Meiosis; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases; C498772:MUS81 protein, human; C498773:Mus81 protein, mouse