Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment

Natsume, Toyoaki, Müller, Carolin A., Katou, Yuki, Retkute, Renata, Gierliński, Marek, Araki, Hiroyuki, Blow, J. Julian, Shirahige, Katsuhiko, Nieduszynski, Conrad A. ORCID: and Tanaka, Tomoyuki U. (2013) Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment. Molecular Cell, 50 (5). pp. 661-674. ISSN 1097-2765

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Centromeres play several important roles in ensuring proper chromosome segregation. Not only do they promote kinetochore assembly for microtubule attachment, but they also support robust sister chromatid cohesion at pericentromeres and facilitate replication of centromeric DNA early in S phase. However, it is still elusive how centromeres orchestrate all these functions at the same site. Here, we show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex. This promptly recruits Sld3-Sld7 replication initiator proteins to pericentromeric replication origins so that they initiate replication early in S phase. Furthermore, DDK at kinetochores independently recruits the Scc2-Scc4 cohesin loader to centromeres in G1 phase. This enhances cohesin loading and facilitates robust pericentromeric cohesion in S phase. Thus, we have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites.

Item Type: Article
Additional Information: Funding Information: We thank K. Nasmyth, A. Marston, and members of the authors’ laboratories for discussions; L. Clayton and B. Wickstead for reading the manuscript; S. Malla, R. Wilson, and M. Blythe for DNA sequencing at DeepSeq; G. Barton for supervising the Data Analysis Group; and K. Natsume and A. Mino for technical help. This work was supported by the Wellcome Trust (grant numbers 081918, 083524, 096535, and 097945), the Medical Research Council (84678), Cancer Research UK (A6996 and A7399), and the Biotechnology and Biological Sciences Research Council (BBSRC; BB/E023754/1 and BB/G001596/1). C.A.N. is a BBSRC David Phillips Fellow. T.U.T. is a Wellcome Trust Principal Research Fellow.
Uncontrolled Keywords: molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 08 Sep 2022 07:31
Last Modified: 21 Oct 2022 01:37
DOI: 10.1016/j.molcel.2013.05.011

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