Abstract

Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. It is well established that Polo-like kinase 1 (Plk1) plays critical roles in mitosis but little is known about its functions at other stages of the cell cycle. Here we summarize the functions of Plk1 during DNA replication, focusing on the molecular events related to Origin Recognition Complex (ORC), the complex that is essential for the initiation of DNA replication. Within the context of Plk1 phosphorylation of Orc2, we also emphasize regulation of Orc2 in different organisms. This review is intended to provide some insight into how Plk1 coordinates DNA replication in S phase with chromosome segregation in mitosis, and orchestrates the cell cycle as a whole.

Highlights

  • Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process

  • DNA replication starts with a series of sequential steps from the formation of pre-replicative complex by Origin Recognition Complex (ORC), which recognizes the origin of DNA replication during G1 phase

  • With the concept of both dormant and active origins along replicating DNA, it is reasonable to speculate that Orc2 stays on chromatin to maintain a dormant origin to counteract DNA replication stress, since it is a critical factor of pre-replicative complex (pre-RC) in cases of depletion of other pre-RC components [39,40]

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Summary

Introduction

Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. The formation of pre-RC and activation of the origin of replication have to be tightly regulated to ensure that DNA replicates only once per cell cycle. In S. cerevisiae , Orc1-6 remain associated with chromatin throughout the cell cycle as a complex [32,33,34,35].

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Conclusion

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