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Protein Phosphatases and DNA Replication Initiation

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The Initiation of DNA Replication in Eukaryotes

Abstract

Eukaryotic DNA replication is controlled by regulated cycles of protein phosphorylation. While the controls over these cycles of kinase activity have been the subject of intense investigation, controls over the removal of phosphorylation, carried out by protein phosphatases, are potentially of equal importance for regulating DNA replication but have in comparison been largely neglected. In this chapter we will first present a brief overview of the families of phosphatases occurring in eukaryotic cells, with emphasis on the PP1 and PP2A subtypes that have been implicated in direct control of replication origin initiation. We will then review our current knowledge of how these phosphatases interact with established control pathways to impact on replication initiation, outlining how PP1 activity is required to prevent premature origin initiation, and its potential involvement in dephosphorylating ORC to enable pre-replication complex formation. Possible pathways for the involvement of PP2A in promoting replication initiation will also be introduced, highlighting the gaps in our understanding and areas of ongoing investigation.

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Acknowledgments

Work in the Donaldson/Hiraga lab is funded by Cancer Research UK grants C1445/A13356 and C1445/A19059, and BBSRC grant K006304/1.

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Authors and Affiliations

  1. Centre for Gene Regulation & Expression, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK

    Michael J. R. Stark

  2. Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

    Shin-ichiro Hiraga & Anne D. Donaldson

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  1. Michael J. R. Stark
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  2. Shin-ichiro Hiraga
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  3. Anne D. Donaldson
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Correspondence to Anne D. Donaldson .

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  1. Florida State Univ. College of Medi, TALLAHASSEE, Florida, USA

    Daniel L. Kaplan

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Stark, M.J.R., Hiraga, Si., Donaldson, A.D. (2016). Protein Phosphatases and DNA Replication Initiation. In: Kaplan, D. (eds) The Initiation of DNA Replication in Eukaryotes. Springer, Cham. https://doi.org/10.1007/978-3-319-24696-3_23

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