dc.contributor.author | Chen, X | |
dc.contributor.author | Ali, YI | |
dc.contributor.author | Fisher, CE | |
dc.contributor.author | Arribas-Bosacoma, R | |
dc.contributor.author | Rajasekaran, MB | |
dc.contributor.author | Williams, G | |
dc.contributor.author | Walker, S | |
dc.contributor.author | Booth, JR | |
dc.contributor.author | Hudson, JJ | |
dc.contributor.author | Roe, SM | |
dc.contributor.author | Pearl, LH | |
dc.contributor.author | Ward, SE | |
dc.contributor.author | Pearl, FM | |
dc.contributor.author | Oliver, AW | |
dc.date.accessioned | 2021-03-31T13:13:53Z | |
dc.date.available | 2021-03-31T13:13:53Z | |
dc.date.issued | 2021-03-01 | |
dc.identifier.citation | eLife, 2021, 10 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4478 | |
dc.identifier.eissn | 2050-084X | |
dc.identifier.doi | 10.7554/elife.65339 | |
dc.description.abstract | BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response; however, selective small molecule inhibitors of defined mechanism are currently lacking. Here, we identify and characterise a specific inhibitor of BLM's ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | eLife Sciences Publications, Ltd | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-02-16 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.7554/elife.65339 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | eLife | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Pearl, Laurence | |