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Kinetochores Coordinate Pericentromeric Cohesion and Early DNA Replication by Cdc7-Dbf4 Kinase Recruitment
- Source :
- Molecular Cell
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • The Ctf19 complex recruits Cdc7-Dbf4 kinase (DDK) to kinetochores (KTs) in telophase • DDK at KTs recruits Sld3–Sld7 to pericentromeric origins, advancing replication timing • DDK at KTs recruits Scc2, enhancing cohesin loading and cohesion at pericentromeres • The DDK functions in replication timing and cohesion are independent of each other
- Subjects :
- DNA Replication
Saccharomyces cerevisiae Proteins
Chromosomal Proteins, Non-Histone
Centromere
Kinetochore assembly
Cell Cycle Proteins
Saccharomyces cerevisiae
Chromatids
Protein Serine-Threonine Kinases
Biology
Article
S Phase
03 medical and health sciences
0302 clinical medicine
Control of chromosome duplication
Kinetochores
Molecular Biology
S phase
030304 developmental biology
Cohesin loading
Genetics
0303 health sciences
Cohesin
Kinetochore
Cell Biology
3. Good health
Cell biology
DNA-Binding Proteins
Establishment of sister chromatid cohesion
Cytoskeletal Proteins
Origin recognition complex
Carrier Proteins
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....16c001a971cb737b02d2ee552f567d00