International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, China.
Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Cancer Sci. 2024 Nov;115(11):3506-3519. doi: 10.1111/cas.16321. Epub 2024 Aug 18.
The fundamental role of cells in safeguarding the genome's integrity against DNA double-strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators.
细胞在保护基因组免受 DNA 双链断裂 (DSB) 方面的基本作用对于维持染色质平衡和整体基因组稳定性至关重要。对 DNA 损伤的异常反应，即 DNA 损伤反应 (DDR)，可导致基因组不稳定，并显著促进肿瘤发生。深入了解严重损伤后 DDR 背后的复杂机制，是为癌症确定治疗靶点的关键。在 DDR 和染色质平衡的背景下，染色质赖氨酸酰化作用（包括乙酰化、乳酰化、丙酰化、丁酰化等多种修饰）已经得到了广泛的研究。在这里，我们深入探讨了修饰酶以及赖氨酸酰化及其相互作用在维持染色质平衡和基因组完整性方面的关键作用，以响应 DDR。此外，我们提供了一个全面的视角和概述，主要由染色质酰化修饰和相关调节剂驱动。
