Role of specific CDKs in regulating DNA damage repair responses and replication stress

Cyclins along with their catalytic units, Cyclin-dependent kinases (CDKs) regulate the cell cycle transition and transcription; and are essentially known as ‘master regulators’ in modulating DNA damage response (DDR) and replication stress. In addition to influencing DNA repair and damage signaling,...

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Published inCurrent opinion in pharmacology Vol. 79; p. 102485
Main Authors Roy, Rahul, Gampa, Siri Chandana, Garimella, Sireesha V.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.12.2024
Subjects
CDKs
Cell cycle
DNA damage response
Inhibitors
Replication stress
Inhibitors
DNA damage response
CDKs
Replication stress
Cell cycle
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Summary:Cyclins along with their catalytic units, Cyclin-dependent kinases (CDKs) regulate the cell cycle transition and transcription; and are essentially known as ‘master regulators’ in modulating DNA damage response (DDR) and replication stress. In addition to influencing DNA repair and damage signaling, CDKs also play a pivotal role in cell division fidelity and the maintenance of genomic integrity after DNA damage. In this review, we focus on the intricate ways by which specific CDKs mainly CDK7, CDK9, and CDK12/13, regulate the cell cycle progression and transcription and how their modulation can lead to lethal effects on the integrity of the genome. With a better knowledge of how these CDKs control the DDR and replication stress, it is now possible to combine CDK inhibitors with chemotherapeutic drugs that damage DNA in ways that can be applied in clinical settings as successful therapeutic strategies.
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ISSN:1471-4892
1471-4973
1471-4973
DOI:10.1016/j.coph.2024.102485