Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.

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 a...

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Autores principales: Lisa Prendergast, Chelly van Vuuren, Agnieszka Kaczmarczyk, Volker Doering, Daniela Hellwig, Nadine Quinn, Christian Hoischen, Stephan Diekmann, Kevin F Sullivan
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spelling oai:doaj.org-article:a8dfbd0ee36d4c4bb9f5318d0d8ea6662021-11-18T05:36:09ZPremitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.1544-91731545-788510.1371/journal.pbio.1001082https://doaj.org/article/a8dfbd0ee36d4c4bb9f5318d0d8ea6662011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21695110/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Centromeres 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.Lisa PrendergastChelly van VuurenAgnieszka KaczmarczykVolker DoeringDaniela HellwigNadine QuinnChristian HoischenStephan DiekmannKevin F SullivanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 6, p e1001082 (2011)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Lisa Prendergast
Chelly van Vuuren
Agnieszka Kaczmarczyk
Volker Doering
Daniela Hellwig
Nadine Quinn
Christian Hoischen
Stephan Diekmann
Kevin F Sullivan
Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
description 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.
format article
author Lisa Prendergast
Chelly van Vuuren
Agnieszka Kaczmarczyk
Volker Doering
Daniela Hellwig
Nadine Quinn
Christian Hoischen
Stephan Diekmann
Kevin F Sullivan
author_facet Lisa Prendergast
Chelly van Vuuren
Agnieszka Kaczmarczyk
Volker Doering
Daniela Hellwig
Nadine Quinn
Christian Hoischen
Stephan Diekmann
Kevin F Sullivan
author_sort Lisa Prendergast
title Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
title_short Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
title_full Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
title_fullStr Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
title_full_unstemmed Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.
title_sort premitotic assembly of human cenps -t and -w switches centromeric chromatin to a mitotic state.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/a8dfbd0ee36d4c4bb9f5318d0d8ea666
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