CDK activity provides temporal and quantitative cues for organizing genome duplication
In: ISSN: 1553-7390, 2018
Online
academicJournal
Zugriff:
International audience ; In eukaryotes, the spatial and temporal organization of genome duplication gives rise to distinctive profiles of replication origin usage along the chromosomes. While it has become increasingly clear that these programs are important for cellular physiology, the mechanisms by which they are determined and modulated remain elusive. Replication initiation requires the function of cyclin-dependent kinases (CDKs), which associate with various cyclin partners to drive cell proliferation. Surprisingly, although we possess detailed knowledge of the CDK regulators and targets that are crucial for origin activation, little is known about whether CDKs play a critical role in establishing the genome-wide pattern of origin selection. We have addressed this question in the fission yeast, taking advantage of a simplified cell cycle network in which cell proliferation is driven by a single cyclin-CDK module. This system allows us to precisely control CDK activity in vivo using chemical genetics. First, in contrast to previous reports, our results clearly show that distinct cyclin-CDK pairs are not essential for regulating specific subsets of origins and for establishing a normal replication program. Importantly, we then demonstrate that the timing at which CDK activity reaches the S phase threshold is critical for the organization of replication in distinct efficiency domains, while the level of CDK activity at the onset of S phase is a dose-dependent modulator of overall origin efficiencies. Our study therefore implicates these different aspects of CDK regulation as versatile mechanisms for shaping the architecture of DNA replication across the genome.
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CDK activity provides temporal and quantitative cues for organizing genome duplication
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Autor/in / Beteiligte Person: | Perrot, Anthony ; Millington, Christopher Lee ; Gomez-Escoda, Blanca ; Schausi-Tiffoche, Diane ; Wu, Pei-Yun Jenny ; Institut de Génétique et Développement de Rennes (IGDR) ; Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1) ; Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES) ; Centre National pour la Recherche Scientific (CNRS) / Institut national de la sante et de la recherche medicale (INSERM) through the ATIP-Avenir program ; Fondation pour la Recherche Medicale (FRM) through the "Amorgage de jeunes equipes" program ; Bretagne, Region ; Fondation, ARC ; Institute of Genetics and Development of Rennes |
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Zeitschrift: | ISSN: 1553-7390, 2018 |
Veröffentlichung: | HAL CCSD ; Public Library of Science, 2018 |
Medientyp: | academicJournal |
DOI: | 10.1371/journal.pgen.1007214 |
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