16 results found
Wigley D, Structure of the DNA-bound spacer capture complex of a Type II CRISPR-Cas system., Molecular Cell, ISSN: 1097-2765
Wilkinson OJ, Martín-González A, Kang H, et al., 2019, CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair, eLife, Vol: 8, ISSN: 2050-084X
CtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. Here we show that human CtIP is a tetrameric protein adopting a dumbbell architecture in which DNA binding domains are connected by long coiled-coils. The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. DNA binding is potentiated by dephosphorylation and is not specific for DNA end structures per se. However, the affinity for linear DNA molecules is increased if the DNA terminates with complex structures including forked ssDNA overhangs and nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks.
Cheng K, Wigley DB, 2018, DNA translocation mechanism of an XPD family helicase, eLife, Vol: 7, ISSN: 2050-084X
The XPD family of helicases, that includes human disease-related FANCJ, DDX11 and RTEL1, are Superfamily 2 helicases that contain an iron-sulphur cluster domain, translocate on ssDNA in a 5'-3' direction and play important roles in genome stability. Consequently, mutations in several of these family members in eukaryotes cause human diseases. Family members in bacteria, such as the DinG helicase from Escherichia coli, are also involved in DNA repair. Here we present crystal structures of complexes of DinG bound to single-stranded DNA (ssDNA) in the presence and absence of an ATP analogue (ADP•BeF3), that suggest a mechanism for 5'-3' translocation along the ssDNA substrate. This proposed mechanism has implications for how those enzymes of the XPD family that recognise bulky DNA lesionsmight stall at these as the first step in initiating DNA repair. Biochemical data reveal roles for conserved residues that are mutated in human diseases.
Willhoft O, Ghoneim M, Lin C-L, et al., 2018, Structure and dynamics of the yeast SWR1-nucleosome complex, SCIENCE, Vol: 362, Pages: 199-+, ISSN: 0036-8075
Ayala R, Willhoft O, Aramayo RJ, et al., 2018, Structure and regulation of the human INO80-nucleosome complex, NATURE, Vol: 556, Pages: 391-+, ISSN: 0028-0836
Aramayo RJ, Willhoft O, Ayala R, et al., 2018, Cryo-EM structures of the human INO80 chromatin-remodeling complex, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 25, Pages: 37-+, ISSN: 1545-9993
Lin C-L, Chaban Y, Rees DM, et al., 2017, Functional characterization and architecture of recombinant yeast SWR1 histone exchange complex, Nucleic Acids Research, Vol: 45, Pages: 7249-7260, ISSN: 0305-1048
Willhoft O, McCormack EA, Aramayo RJ, et al., 2017, Crosstalk within a functional INO80 complex dimer regulates nucleosome sliding, ELIFE, Vol: 6, ISSN: 2050-084X
Sanders K, Lin C-L, Smith AJ, et al., 2017, The structure and function of an RNA polymerase interaction domain in the PcrA/UvrD helicase, Nucleic Acids Research, Vol: 45, Pages: 3875-3887, ISSN: 0305-1048
Rees DM, Willhoft O, Lin C-L, et al., 2017, Production and Assay of Recombinant Multisubunit Chromatin Remodeling Complexes, DNA REPAIR ENZYMES: STRUCTURE, BIOPHYSICS, AND MECHANISM, Vol: 592, Pages: 27-47, ISSN: 0076-6879
Wilkinson M, Troman L, Wan Nur Ismah WAK, et al., 2016, Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones, eLife, Vol: 5
Willhoft O, Bythell-Douglas R, McCormack EA, et al., 2016, Synergy and antagonism in regulation of recombinant human INO80 chromatin remodeling complex, NUCLEIC ACIDS RESEARCH, Vol: 44, Pages: 8179-8188, ISSN: 0305-1048
Wilkinson M, Chaban Y, Wigley DB, 2016, Mechanism for nuclease regulation in RecBCD, eLife, Vol: 5
Krajewski WW, Fu X, Wilkinson M, et al., 2014, Structural basis for translocation by AddAB helicase–nuclease and its arrest at χ sites, Nature, Vol: 508, Pages: 416-419, ISSN: 0028-0836
Saravanan M, Wuerges J, Bose D, et al., 2012, Interactions between the nucleosome histone core and Arp8 in the INO80 chromatin remodeling complex, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 20883-20888, ISSN: 0027-8424
Zhang X, Wigley DB, 2008, The 'glutamate switch' provides a link between ATPase activity and ligand binding in AAA plus proteins, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 15, Pages: 1223-1227, ISSN: 1545-9993
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