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Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition
Author(s) -
Newman Matthew,
MurrayRust Judith,
Lally John,
Rudolf Jana,
Fadden Andrew,
Knowles Philip P,
White Malcolm F,
McDonald Neil Q
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600581
Subject(s) - library science , original research , sociology , art history , history , computer science
The XPF/Mus81 structure‐specific endonucleases cleave double‐stranded DNA (dsDNA) within asymmetric branched DNA substrates and play an essential role in nucleotide excision repair, recombination and genome integrity. We report the structure of an archaeal XPF homodimer alone and bound to dsDNA. Superposition of these structures reveals a large domain movement upon binding DNA, indicating how the (HhH) 2 domain and the nuclease domain are coupled to allow the recognition of double‐stranded/single‐stranded DNA junctions. We identify two nonequivalent DNA‐binding sites and propose a model in which XPF distorts the 3′ flap substrate in order to engage both binding sites and promote strand cleavage. The model rationalises published biochemical data and implies a novel role for the ERCC1 subunit of eukaryotic XPF complexes.