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Premitotic Assembly of Human CENPs -T and -W Switches Centromeric Chromatin to a Mitotic State.

ARAN - Access to Research at NUI Galway

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dc.contributor.author Prendergast, Lisa
dc.contributor.author van Vuuren, Chelly
dc.contributor.author Kaczmarczyk, Agnieszka
dc.contributor.author Quinn, Nadine
dc.contributor.author Sullivan, Kevin F.
dc.date.accessioned 2012-04-30T16:32:05Z
dc.date.available 2012-04-30T16:32:05Z
dc.date.issued 2011
dc.identifier.citation Prendergast L, van Vuuren C, Kaczmarczyk A, Doering V, Hellwig D, Quinn N, Hoischen C, Diekmann S, Sullivan KF. (2011) 'Premitotic Assembly of Human CENPs -T and -W Switches Centromeric Chromatin to a Mitotic State'. Plos Biol, . en_US
dc.identifier.uri http://hdl.handle.net/10379/2705
dc.description.abstract Centromeres are differentiated chromatin domains, present once per chromosome, that direct segregation of the genome in mitosis and meiosis by specifying assembly of the kinetochore. They are distinct genetic loci in that their identity in most organisms is determined not by the DNA sequences they are associated with, but through specific chromatin composition and context. The core nucleosomal protein CENP-A/cenH3 plays a primary role in centromere determination in all species and directs assembly of a large complex of associated proteins in vertebrates. While CENP-A itself is stably transmitted from one generation to the next, the nature of the template for centromere replication and its relationship to kinetochore function are as yet poorly understood. Here, we investigate the assembly and inheritance of a histone fold complex of the centromere, the CENP-T/W complex, which is integrated with centromeric chromatin in association with canonical histone H3 nucleosomes. We have investigated the cell cycle regulation, timing of assembly, generational persistence, and requirement for function of CENPs -T and -W in the cell cycle in human cells. The CENP-T/W complex assembles through a dynamic exchange mechanism in late S-phase and G2, is required for mitosis in each cell cycle and does not persist across cell generations, properties reciprocal to those measured for CENP-A. We propose that the CENP-A and H3-CENP-T/W nucleosome components of the centromere are specialized for centromeric and kinetochore activities, respectively. Segregation of the assembly mechanisms for the two allows the cell to switch between chromatin configurations that reciprocally support the replication of the centromere and its conversion to a mitotic state on postreplicative chromatin. en_US
dc.description.sponsorship SFI en_US
dc.format application/pdf en_US
dc.language.iso en en_US
dc.relation.ispartof Plos Biol en
dc.subject Chromosome biology en_US
dc.title Premitotic Assembly of Human CENPs -T and -W Switches Centromeric Chromatin to a Mitotic State. en_US
dc.type Article en_US
dc.date.updated 2012-04-30T16:23:23Z
dc.identifier.doi 10.1371/journal.pbio.1001082
dc.description.peer-reviewed peer-reviewed
dc.contributor.funder |~|SFI|~|
dc.internal.rssid 1171379
dc.local.contact Kevin Sullivan, Biochemistry, Nui Galway. 2434 Email: kevin.sullivan@nuigalway.ie
dc.local.copyrightchecked Yes
dc.local.version ACCEPTED

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