DNA损伤反应的表观遗传编排：对调节机制的见解
Epigenetic orchestration of the DNA damage response: Insights into the regulatory mechanisms
影响因子:6.42000
发表日期:2024
作者:
Atanu Mondal, Agniswar Sarkar, Dipanwita Das, Amrita Sengupta, Aindrila Kabiraj, Payel Mondal, Rachayita Nag, Shravanti Mukherjee, Chandrima Das
摘要
DNA损伤反应（DDR）是一种关键细胞机制，可保护基因组完整性并防止有害DNA病变的积累。越来越多的证据突出了DDR信号传导与表观遗传调节之间的相交，从而深刻了解了细胞功能的各个方面，包括肿瘤发生。这项全面的综述探讨了表观遗传修饰与DDR激活之间的复杂关系，并特别关注病毒感染的影响。已证明致癌病毒，例如人乳头瘤病毒，肝炎病毒（HBV或HCV）和爱泼斯坦 - 巴尔病毒可激活DDR。因此，这些DNA损伤事件触发了一系列表观遗传学改变，包括DNA甲基化模式的变化，组蛋白的修饰和非编码RNA的表达。这些表观遗传变化对染色质结构，基因表达和基因组稳定性的维持产生了深远的影响。重要的是，在DDR背景下，阐明病毒诱导的表观遗传学改变对理解癌症的复杂性具有重要意义，并为治疗干预提供了潜在的靶标。
Abstract
The DNA damage response (DDR) is a critical cellular mechanism that safeguards genome integrity and prevents the accumulation of harmful DNA lesions. Increasing evidence highlights the intersection between DDR signaling and epigenetic regulation, offering profound insights into various aspects of cellular function including oncogenesis. This comprehensive review explores the intricate relationship between the epigenetic modifications and DDR activation, with a specific focus on the impact of viral infections. Oncogenic viruses, such as human papillomavirus, hepatitis virus (HBV or HCV), and Epstein-Barr virus have been shown to activate the DDR. Consequently, these DNA damage events trigger a cascade of epigenetic alterations, including changes in DNA methylation patterns, histone modifications and the expression of noncoding RNAs. These epigenetic changes exert profound effects on chromatin structure, gene expression, and maintenance of genome stability. Importantly, elucidation of the viral-induced epigenetic alterations in the context of DDR holds significant implications for comprehending the complexity of cancer and provides potential targets for therapeutic interventions.