Kumari Nitu, Kaur Ekjot, Raghavan Sathees C, Sengupta Sagar
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
Biotechnology Research and Innovation Council - National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India.
Curr Opin Pharmacol. 2025 Feb;80:102496. doi: 10.1016/j.coph.2024.102496. Epub 2024 Dec 9.
DNA damage signaling is a highly coordinated cellular process which is required for the removal of DNA lesions. Amongst the different types of DNA damage, double-strand breaks (DSBs) are the most harmful type of lesion that attenuates cellular proliferation. DSBs are repaired by two major pathways-homologous recombination (HR), and non-homologous end-joining (NHEJ) and in some cases by microhomology-mediated end-joining (MMEJ). Preference of the pathway depends on multiple parameters including site of the DNA damage, the cell cycle phase and topology of the DNA lesion. Deregulated repair response contributes to genomic instability resulting in a plethora of diseases including cancer. This review discusses the different molecular players of HR, NHEJ, and MMEJ pathways that control the switch among the different DSB repair pathways. We also highlight the various functions of chromatin modifications in modulating repair response and how deregulated DNA damage repair response may promote oncogenic transformation.
DNA损伤信号传导是一个高度协调的细胞过程，是清除DNA损伤所必需的。在不同类型的DNA损伤中，双链断裂（DSB）是最有害的损伤类型，会减弱细胞增殖。DSB通过两种主要途径修复——同源重组（HR）和非同源末端连接（NHEJ），在某些情况下通过微同源性介导的末端连接（MMEJ）。修复途径的偏好取决于多个参数，包括DNA损伤的位点、细胞周期阶段和DNA损伤的拓扑结构。失调的修复反应会导致基因组不稳定，从而引发包括癌症在内的多种疾病。本综述讨论了HR、NHEJ和MMEJ途径中控制不同DSB修复途径之间转换的不同分子参与者。我们还强调了染色质修饰在调节修复反应中的各种功能，以及失调的DNA损伤修复反应如何促进致癌转化。
