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Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast

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  • Philip Zegerman

    (Clare Hall Laboratories)

  • John F. X. Diffley

    (Clare Hall Laboratories)

Abstract

Cyclin-dependent kinases (CDKs) drive major cell cycle events including the initiation of chromosomal DNA replication. We identified two S phase CDK (S-CDK) phosphorylation sites in the budding yeast Sld3 protein that, together, are essential for DNA replication. Here we show that, when phosphorylated, these sites bind to the amino-terminal BRCT repeats of Dpb11. An Sld3–Dpb11 fusion construct bypasses the requirement for both Sld3 phosphorylation and the N-terminal BRCT repeats of Dpb11. Co-expression of this fusion with a phospho-mimicking mutant in a second essential CDK substrate, Sld2, promotes DNA replication in the absence of S-CDK. Therefore, Sld2 and Sld3 are the minimal set of S-CDK targets required for DNA replication. DNA replication in cells lacking G1 phase CDK (G1-CDK) required expression of the Cdc7 kinase regulatory subunit, Dbf4, as well as Sld2 and Sld3 bypass. Our results help to explain how G1- and S-CDKs promote DNA replication in yeast.

Suggested Citation

  • Philip Zegerman & John F. X. Diffley, 2007. "Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast," Nature, Nature, vol. 445(7125), pages 281-285, January.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7125:d:10.1038_nature05432
    DOI: 10.1038/nature05432
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    Cited by:

    1. Juan Manuel Valverde & Geronimo Dubra & Michael Phillips & Austin Haider & Carlos Elena-Real & Aurélie Fournet & Emile Alghoul & Dhanvantri Chahar & Nuria Andrés-Sanchez & Matteo Paloni & Pau Bernadó , 2023. "A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Matthew Day & Bilal Tetik & Milena Parlak & Yasser Almeida-Hernández & Markus Räschle & Farnusch Kaschani & Heike Siegert & Anika Marko & Elsa Sanchez-Garcia & Markus Kaiser & Isabel A. Barker & Laure, 2024. "TopBP1 utilises a bipartite GINS binding mode to support genome replication," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Anna C. Papageorgiou & Michaela Pospisilova & Jakub Cibulka & Raghib Ashraf & Christopher A. Waudby & Pavel Kadeřávek & Volha Maroz & Karel Kubicek & Zbynek Prokop & Lumir Krejci & Konstantinos Tripsi, 2023. "Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Karl-Uwe Reusswig & Julia Bittmann & Martina Peritore & Mathilde Courtes & Benjamin Pardo & Michael Wierer & Matthias Mann & Boris Pfander, 2022. "Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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