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Cited by 59DNA Repair MechanismsCancer-related Molecular PathwaysMicrotubule and mitosis dynamics

Human CDK18 promotes replication stress signaling and genome stability

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Barone, Giancarlo, Staples, Christopher J., Ganesh, Anil, Patterson, Karl W., Bryne, Dominic P., Myers, Katie N., Patil, Abhijit A., Eyers, Claire E. +4 more·2016·Nucleic Acids Research
DOI 10.1093/nar/gkw615PMC PMC5062979
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Abstract

Cyclin-dependent kinases (CDKs) coordinate cell cycle checkpoints with DNA repair mechanisms that together maintain genome stability. However, the myriad mechanisms that can give rise to genome instability are still to be fully elucidated. Here, we identify CDK18 (PCTAIRE 3) as a novel regulator of genome stability, and show that depletion of CDK18 causes an increase in endogenous DNA damage and chromosomal abnormalities. CDK18-depleted cells accumulate in early S-phase, exhibiting retarded replication fork kinetics and reduced ATR kinase signaling in response to replication stress. Mechanistically, CDK18 interacts with RAD9, RAD17 and TOPBP1, and CDK18-deficiency results in a decrease in both RAD17 and RAD9 chromatin retention in response to replication stress. Importantly, we demonstrate that these phenotypes are rescued by exogenous CDK18 in a kinase-dependent manner. Collectively, these data reveal a rate-limiting role for CDK18 in replication stress signalling and establish it as a novel regulator of genome integrity.

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  • Cdk18 is a cyclin-dependent kinase that usually functions to clear DNA damages.

    “It led to higher expression of Cdk18 which is a cyclin-dependent kinase and usually functions to clear DNA damages88.”

    From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [88]

    The Introduction identifies CDK18 as a cyclin-dependent kinase. The Results report that CDK18-depleted cells accumulate DNA damage and cannot efficiently repair DNA breaks by homologous recombination. This supports a role in the DNA-damage response, but the paper characterizes CDK18 chiefly as a regulator of replication-stress signaling, not as a kinase that usually clears DNA damage. (LLM, conf=0.84)

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Authors
Barone, G., Staples, C. J., Ganesh, A., Patterson, K. W., Bryne, D. P., Myers, K. N., Patil, A. A., Eyers, C. E., Maslen, S., Skehel, J. M., Eyers, P. A., & Collis, S. J.
Affiliations
  • University of Sheffield (GB)
  • University of Liverpool (GB)
  • MRC Laboratory of Molecular Biology (GB)
Corresponding author
Collis, Spencer J.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2016-07-05
Volume
44
Issue
18
Pages
8772-8785
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkw615
PMC
PMC5062979
OpenAlex
W2466366317
Cited by
59
References
7
Citations by year
2026: 9 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 1
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Cancer Research Institute
  • Cancer Research UK (A12102, 12102)
  • North West Cancer Research (CR1037)
  • University of Oxford
  • Biotechnology and Biological Sciences Research Council (BB/L009501/1, BB/M012557/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
cyclin-dependent kinases, replication stress, genome stability, ATR signaling, Rad9, Rad17, TopBP1, S-phase checkpoint, chromosomal abnormalities, DNA damage, kinase activity
MeSH terms
Chromatin, Chromosome Aberrations, DNA Damage, DNA Replication, Humans, Phosphorylation, Protein Binding, Stress, Physiological, Signal Transduction, Cell Cycle Proteins, Cyclin-Dependent Kinases, RNA Interference, RNA, Small Interfering, Genomic Instability, Cell Line, Tumor, Protein Interaction Domains and Motifs, Cell Cycle Checkpoints

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