Abstract

The fission yeast centromere, which is similar to metazoan centromeres, contains highly repetitive pericentromere sequences that are assembled into heterochromatin. This is required for the recruitment of cohesin and proper chromosome segregation. Surprisingly, the pericentromere replicates early in the S phase. Loss of heterochromatin causes this domain to become very sensitive to replication fork defects, leading to gross chromosome rearrangements. This review examines the interplay between components of DNA replication, heterochromatin assembly, and cohesin dynamics that ensures maintenance of genome stability and proper chromosome segregation.

Highlights

  • The centromere is the structural domain on the chromosome required for proper attachment of the spindle

  • The pericentromeres in S. pombe contain long tracts of repeated sequences that are protected by classic heterochromatin, including histone H3K9 methylation and the binding of Swi6, a homologue of heterochromatin protein 1 (HP-1)

  • The heterochromatin is cyclically disrupted during mitosis and re-formed during DNA replication

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Summary

Introduction

The centromere is the structural domain on the chromosome required for proper attachment of the spindle (reviewed in [1]). Swi is essential for the recruitment of cohesin to the centromere, which is required for proper kinetochore attachment and chromosome segregation [22,23]. Both early replication and cohesion depend on the replication kinase DDK (DBF4 dependent kinase) [19,24]; replication dynamics are intimately involved in centromere function. Destabilizing the replication fork in cells lacking Swi enhances rearrangements and chromosome loss [14]. Together, these observations emphasize that the centromere is a fragile element in the genome. This review describes work largely from the fission yeast Schizosaccharomyces pombe, to examine how replication progression and centromere structure interact to maintain genome stability in this region

Assembly and Activation of the Replisome
DNA Replication Stress Causes Genome Instability
Centromere Structure
Early Replication in the Centromere
Genome Stress in the Centromere
Cohesion
Conclusions

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