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Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

Cohesin is a conserved ring-shaped multiprotein complex that participates in chromosome segregation, DNA repair, and transcriptional regulation [1, 2]. Cohesin loading onto chromosomes universally requires the Scc2/4 “loader” complex (also called NippedBL/Mau2), mutations in which cause the developm...

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Autores principales: Fernius, Josefin, Nerusheva, Olga O., Galander, Stefan, Alves, Flavia de Lima, Rappsilber, Juri, Marston, Adele L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627958/
https://www.ncbi.nlm.nih.gov/pubmed/23499533
http://dx.doi.org/10.1016/j.cub.2013.02.022
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author Fernius, Josefin
Nerusheva, Olga O.
Galander, Stefan
Alves, Flavia de Lima
Rappsilber, Juri
Marston, Adele L.
author_facet Fernius, Josefin
Nerusheva, Olga O.
Galander, Stefan
Alves, Flavia de Lima
Rappsilber, Juri
Marston, Adele L.
author_sort Fernius, Josefin
collection PubMed
description Cohesin is a conserved ring-shaped multiprotein complex that participates in chromosome segregation, DNA repair, and transcriptional regulation [1, 2]. Cohesin loading onto chromosomes universally requires the Scc2/4 “loader” complex (also called NippedBL/Mau2), mutations in which cause the developmental disorder Cornelia de Lange syndrome in humans [1–9]. Cohesin is most concentrated in the pericentromere, the region surrounding the centromere [10–15]. Enriched pericentromeric cohesin requires the Ctf19 kinetochore subcomplex in budding yeast [16–18]. Here, we uncover the spatial and temporal determinants for Scc2/4 centromere association. We demonstrate that the critical role of the Ctf19 complex is to enable Scc2/4 association with centromeres, through which cohesin loads and spreads onto the adjacent pericentromere. We show that, unexpectedly, Scc2 association with centromeres depends on cohesin itself. The absence of the Scc1/Mcd1/Rad21 cohesin subunit precludes Scc2 association with centromeres from anaphase until late G1. Expression of SCC1 is both necessary and sufficient for the binding of cohesin to its loader, the association of Scc2 with centromeres, and cohesin loading. We propose that cohesin triggers its own loading by enabling Scc2/4 to connect with chromosomal landmarks, which at centromeres are specified by the Ctf19 complex. Overall, our findings provide a paradigm for the spatial and temporal control of cohesin loading.
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spelling pubmed-36279582013-04-17 Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment Fernius, Josefin Nerusheva, Olga O. Galander, Stefan Alves, Flavia de Lima Rappsilber, Juri Marston, Adele L. Curr Biol Report Cohesin is a conserved ring-shaped multiprotein complex that participates in chromosome segregation, DNA repair, and transcriptional regulation [1, 2]. Cohesin loading onto chromosomes universally requires the Scc2/4 “loader” complex (also called NippedBL/Mau2), mutations in which cause the developmental disorder Cornelia de Lange syndrome in humans [1–9]. Cohesin is most concentrated in the pericentromere, the region surrounding the centromere [10–15]. Enriched pericentromeric cohesin requires the Ctf19 kinetochore subcomplex in budding yeast [16–18]. Here, we uncover the spatial and temporal determinants for Scc2/4 centromere association. We demonstrate that the critical role of the Ctf19 complex is to enable Scc2/4 association with centromeres, through which cohesin loads and spreads onto the adjacent pericentromere. We show that, unexpectedly, Scc2 association with centromeres depends on cohesin itself. The absence of the Scc1/Mcd1/Rad21 cohesin subunit precludes Scc2 association with centromeres from anaphase until late G1. Expression of SCC1 is both necessary and sufficient for the binding of cohesin to its loader, the association of Scc2 with centromeres, and cohesin loading. We propose that cohesin triggers its own loading by enabling Scc2/4 to connect with chromosomal landmarks, which at centromeres are specified by the Ctf19 complex. Overall, our findings provide a paradigm for the spatial and temporal control of cohesin loading. Cell Press 2013-04-08 /pmc/articles/PMC3627958/ /pubmed/23499533 http://dx.doi.org/10.1016/j.cub.2013.02.022 Text en © 2013 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Report
Fernius, Josefin
Nerusheva, Olga O.
Galander, Stefan
Alves, Flavia de Lima
Rappsilber, Juri
Marston, Adele L.
Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title_full Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title_fullStr Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title_full_unstemmed Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title_short Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment
title_sort cohesin-dependent association of scc2/4 with the centromere initiates pericentromeric cohesion establishment
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627958/
https://www.ncbi.nlm.nih.gov/pubmed/23499533
http://dx.doi.org/10.1016/j.cub.2013.02.022
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