DDK: The outsourced kinase of chromosome maintenance

Gillespie, Peter J. and Blow, J. Julian (2022) DDK: The outsourced kinase of chromosome maintenance. Biology-Basel, 11 (6). ISSN 2079-7737

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The maintenance of genomic stability during the mitotic cell-cycle not only demands that the DNA is duplicated and repaired with high fidelity, but that following DNA replication the chromatin composition is perpetuated and that the duplicated chromatids remain tethered until their anaphase segregation. The coordination of these processes during S phase is achieved by both cyclin-dependent kinase, CDK, and Dbf4-dependent kinase, DDK. CDK orchestrates the activation of DDK at the G1-to-S transition, acting as the 'global' regulator of S phase and cell-cycle progression, whilst 'local' control of the initiation of DNA replication and repair and their coordination with the re-formation of local chromatin environments and the establishment of chromatid cohesion are delegated to DDK. Here, we discuss the regulation and the multiple roles of DDK in ensuring chromosome maintenance. Regulation of replication initiation by DDK has long been known to involve phosphorylation of MCM2-7 subunits, but more recent results have indicated that Treslin:MTBP might also be important substrates. Molecular mechanisms by which DDK regulates replisome stability and replicated chromatid cohesion are less well understood, though important new insights have been reported recently. We discuss how the 'outsourcing' of activities required for chromosome maintenance to DDK allows CDK to maintain outright control of S phase progression and the cell-cycle phase transitions whilst permitting ongoing chromatin replication and cohesion establishment to be completed and achieved faithfully.

Item Type: Article
Additional Information: Funding Information: Funding: This work was in part supported by CR-UK programme grant C303/A14301 and Wellcome Trust Investigator award WT096598MA. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Uncontrolled Keywords: ddk,cdk,dna replication,replication fork stability,dna repair,chromatid cohesion,epigenetic inheritance,agricultural and biological sciences(all),biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/1100
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Depositing User: LivePure Connector
Date Deposited: 10 Jun 2024 11:30
Last Modified: 15 Jul 2024 12:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/95448
DOI: 10.3390/biology11060877

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