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dc.contributor.authorRichards, MW
dc.contributor.authorLeung, JWC
dc.contributor.authorRoe, SM
dc.contributor.authorLi, K
dc.contributor.authorChen, J
dc.contributor.authorBayliss, R
dc.date.accessioned2018-08-24T08:25:54Z
dc.date.issued2010-02-05
dc.identifier5
dc.identifier.citationJOURNAL OF MOLECULAR BIOLOGY, 2010, 395 pp. 908 - 915
dc.identifier.issn0022-2836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2380
dc.identifier.doi10.1016/j.jmb.2009.11.029
dc.description.abstractMcph1 is mutated in autosomal recessive primary microcephaly and premature chromosome condensation (PCC) syndrome. Increased chromosome condensation is a common feature of cells isolated from patients afflicted with either disease. Normal cells depleted of Mcph1 also exhibit PCC phenotype. Human Mcph1 contains three BRCA1-carboxyl terminal (BRCT) domains, the first of which (Mcph1N) is necessary for the prevention of PCC. The only known disease-associated missense mutation in Mcph1 resides in this domain (T27R). We have determined the X-ray crystal structure of human Mcph1N to 16 angstrom resolution Compared with other BRCT domain structures, the most striking differences are an elongated, ordered beta 1-alpha 1 loop and an adjacent hydrophobic pocket This pocket is in the equivalent structural position to the phosphate binding site of BRCT domains that recognize phospho-proteins, although the phosphate-binding residues are absent in Mcph1N. Mutations in the pocket abrogate the ability of full-length Mcph1 to rescue the PCC phenotype of Mcph1(-/) mouse embryonic fibroblast cells, suggesting that it forms an essential part of a protein-protein interaction site necessary to prevent PCC. (C) 2009 Elsevier Ltd. All rights reserved
dc.format.extent908 - 915
dc.languageeng
dc.language.isoeng
dc.publisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
dc.titleA Pocket on the Surface of the N-Terminal BRCT Domain of Mcph1 Is Required to Prevent Abnormal Chromosome Condensation
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/j.jmb.2009.11.029
rioxxterms.licenseref.startdate2010-02-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJOURNAL OF MOLECULAR BIOLOGY
pubs.notesaffiliation: Bayliss, R (Reprint Author), Inst Canc Res, Sect Struct Biol, Chester Beatty Labs, 237 Fulham Rd, London SW3 6JB, England. Richards, Mark W.; Roe, S. Mark; Bayliss, Richard, Inst Canc Res, Sect Struct Biol, Chester Beatty Labs, London SW3 6JB, England. Leung, Justin W. C.; Chen, Junjie, Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Li, Kaiyi, Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. keywords: microcephaly; Mcph1; BRCT domain; premature chromosome condensation; X-ray crystallography keywords-plus: DNA-DAMAGE RESPONSE; CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; PROTEIN; MICROCEPHALIN; PHOSPHOPEPTIDE; CANCER; RECOGNITION; SOFTWARE; REPEATS research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology orcid-numbers: Bayliss, Richard/0000-0003-0604-2773 Richards, Mark/0000-0003-1108-2825 funding-acknowledgement: Royal Society University Research Fellowship; Cancer Research UK [C24461/A8032, C24461/A9549]; Medical Research Council [G0800021]; Career Development Faculty Programme of The Institute of Cancer Research; Cancer Research UK for Structural Biology at ICR; NHS; National Institutes of Health; Department of Defense funding-text: R.B acknowledges the support of a Royal Society University Research Fellowship, Cancer Research UK (C24461/A8032, C24461/A9549), the Medical Research Council (G0800021), the Career Development Faculty Programme of The Institute of Cancer Research, infrastructural support from Cancer Research UK for Structural Biology at ICR, and NHS funding to the NIHR Biomedical Research Centre. J.C. was supported by grants from the National Institutes of Health. J.C. is also a recipient of an Era of Hope Scholar award from the Department of Defense and a member of the Mavo Clinic Breast SPORE program. We are indebted to the staff of DIAMOND beamline 103 for their support during data collection and to the ISMB Biophysics Centre at Birkbeck, University of London, UK for use of their circular dichroism instrument. number-of-cited-references: 33 times-cited: 8 usage-count-last-180-days: 0 usage-count-since-2013: 1 journal-iso: J. Mol. Biol. doc-delivery-number: 560SJ unique-id: ISI:000274922400002 oa: green_accepted da: 2018-08-23
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume395
pubs.embargo.termsNot known
dc.contributor.icrauthorBayliss, Richard


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