特定 CDK 在调节 DNA 损伤修复反应和复制压力中的作用

IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY Current Opinion in Pharmacology Pub Date : 2024-09-10 DOI:10.1016/j.coph.2024.102485
Rahul Roy , Siri Chandana Gampa , Sireesha V. Garimella
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引用次数: 0

摘要

细胞周期蛋白及其催化单元--细胞周期蛋白依赖性激酶(CDKs)调控细胞周期的转换和转录,被称为调节 DNA 损伤反应(DDR)和复制应激的 "主调节器"。除了影响 DNA 修复和损伤信号转导外,CDK 还在 DNA 损伤后细胞分裂的保真度和基因组完整性的维护方面发挥着关键作用。在这篇综述中,我们将重点关注特定 CDK(主要是 CDK7、CDK9 和 CDK12/13)调控细胞周期进程和转录的复杂方式,以及它们的调控如何导致对基因组完整性的致命影响。随着人们对这些 CDK 如何控制 DDR 和复制应激有了更深入的了解,现在有可能将 CDK 抑制剂与损伤 DNA 的化疗药物结合起来,作为成功的治疗策略应用于临床。
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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, 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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来源期刊
CiteScore
8.80
自引率
2.50%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.
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