Abstract
SummaryCentromeres 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.
Highlights
The centromere promotes the assembly of the kinetochore, which provides the major attachment site for spindle microtubules and ensures faithful chromosome segregation during mitosis
We show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex
We have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites
Summary
The centromere promotes the assembly of the kinetochore, which provides the major attachment site for spindle microtubules and ensures faithful chromosome segregation during mitosis. This is not the only function of the centromere; it plays at least two additional important roles. When a centromere is transferred to a new chromosome locus in S. cerevisiae, all the above features of the centromere are re-established at the new site (Hill and Bloom, 1989; Pohl et al, 2012; Tanaka et al, 1999), indicating that the centromere suffices for these functions. It is not known how the centromere orchestrates all these functions at the same site
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