Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea.
Int J Mol Sci. 2023 Jun 16;24(12):10212. doi: 10.3390/ijms241210212.
DNA double-strand breaks (DSBs) are the most lethal DNA damages which lead to severe genome instability. Phosphorylation is one of the most important protein post-translation modifications involved in DSBs repair regulation. Kinases and phosphatases play coordinating roles in DSB repair by phosphorylating and dephosphorylating various proteins. Recent research has shed light on the importance of maintaining a balance between kinase and phosphatase activities in DSB repair. The interplay between kinases and phosphatases plays an important role in regulating DNA-repair processes, and alterations in their activity can lead to genomic instability and disease. Therefore, study on the function of kinases and phosphatases in DSBs repair is essential for understanding their roles in cancer development and therapeutics. In this review, we summarize the current knowledge of kinases and phosphatases in DSBs repair regulation and highlight the advancements in the development of cancer therapies targeting kinases or phosphatases in DSBs repair pathways. In conclusion, understanding the balance of kinase and phosphatase activities in DSBs repair provides opportunities for the development of novel cancer therapeutics.
DNA 双链断裂 (DSBs) 是最致命的 DNA 损伤，可导致严重的基因组不稳定性。磷酸化是参与 DSBs 修复调控的最重要的蛋白质翻译后修饰之一。激酶和磷酸酶通过磷酸化和去磷酸化各种蛋白质在 DSB 修复中发挥协调作用。最近的研究揭示了在 DSB 修复中维持激酶和磷酸酶活性平衡的重要性。激酶和磷酸酶之间的相互作用在调节 DNA 修复过程中起着重要作用，其活性的改变可导致基因组不稳定和疾病。因此，研究激酶和磷酸酶在 DSBs 修复中的功能对于理解它们在癌症发展和治疗中的作用至关重要。在这篇综述中，我们总结了目前关于 DSBs 修复调控中激酶和磷酸酶的知识，并强调了针对 DSBs 修复途径中的激酶或磷酸酶开发癌症治疗方法的最新进展。总之，了解 DSBs 修复中激酶和磷酸酶活性的平衡为开发新型癌症治疗方法提供了机会。
