Abstract

The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment. Two additional functions of the centromere, however, are becoming increasingly clear: facilitation of robust sister-chromatid cohesion at pericentromeres and advancement of replication of centromeric regions. The combination of these three centromere functions ensures correct chromosome segregation during mitosis. Here, we review the mechanisms of the kinetochore-microtubule interaction, focusing on sister-kinetochore bi-orientation (or chromosome bi-orientation). We also discuss the biological importance of robust pericentromeric cohesion and early centromere replication, as well as the mechanisms orchestrating these two functions at the microtubule attachment site.

Highlights

  • The centromere is a specialized chromosome site that has essential roles in chromosome segregation

  • Budding yeast Aurora B kinase promotes the turnover of kinetochore–microtubule attachment when there is no tension, for example on syntelic attachment, in which both sister kinetochores attach to microtubules from the same spindle pole (Fig 2; [25,26])

  • Sidebar A | In need of answers (i) How is the kinetochore–microtubule interaction stabilized when sister-kinetochore bi-orientation is established? (ii) How does robust pericentromeric cohesion promote sister-kinetochore bi-orientation? (iii) What is the advantage of early DNA replication of centromeric regions? (iv) How evolutionarily conserved is the centromere function of advancing the DNA replication timing of centromeric regions? (v) How does DDK promote pericentromeric cohesion and advance DNA

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Summary

OPEN ACCESS rreevviieeww

The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment. Two additional functions of the centromere, are becoming increasingly clear: facilitation of robust sister-chromatid cohesion at peric­entromeres and advancement of replication of centromeric regions. The combination of these three centromere functions ensures correct chromosome segregation during mitosis. We review the mechanisms of the kinetochore–microtubule interaction, focusing on sister-­ kinetochore bi-orientation (or chromosome bi-orientation). We discuss the biological importance of robust peri­centromeric cohesion and early centromere replication, as well as the mechanisms orchestrating these two functions at the microtubule attachment site.

Introduction
Centromeres promote interaction with spindle microtubules
Replication origins around centromeres
Aurora B kinase
Kinetochore CEN
Centromeres facilitate robust pericentromeric cohesion
Cohesin enrichment in budding yeast
Replication initiation in early S phase
DDK at kinetochores
The centromere advances its replication timing
Conclusions and perspectives
Full Text
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