Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.
Int J Mol Sci. 2022 Mar 24;23(7):3555. doi: 10.3390/ijms23073555.
Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.
细胞周期蛋白依赖性激酶（CDKs）是 DNA 损伤反应（DDR）的关键介质和效应物，调节参与修复过程的途径成分和蛋白质。合成致死性（SL）描述了这样一种情况，即两个基因以这样的方式联系在一起，以至于仅仅缺乏一个基因的功能就能维持细胞活力，而耗尽两个基因则会引发细胞死亡。现在已经出现了涉及 CDKs 的合成致死相互作用，这可以用于选择性地靶向具有 DNA 修复缺陷的肿瘤细胞。在这篇综述中，讨论了 CDK 与原癌基因产物 MYC、多聚（ADP-核糖）聚合酶（PARP-1）和细胞肿瘤抗原 p53（TP53）的 SL 相互作用。描述了每个 SL 伙伴在 DDR 中的单独作用。
