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.
London Research Institute, Cancer Research UK, Clare Hall Laboratories, Hertfordshire, United Kingdom.
Alberto
A
Ciccia
Neil
N
McDonald
Stephen C
SC
West
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