Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Natsume T,Müller CA,Katou Y,Retkute R,Gierliński M,Araki H,Blow JJ,Shirahige K,Nieduszynski CA,Tanaka TUdoi
10.1016/j.molcel.2013.05.011subject
Has Abstractpub_date
2013-06-06 00:00:00pages
661-74issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(13)00374-2journal_volume
50pub_type
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