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细胞在长期进化过程中形成的DNA损伤反应防御机制包括转录调节、周期调控、损伤修复、凋亡性和非凋亡性死亡等的一系列细胞学反应,是基因组稳定性维持的基石。其调控异常与肿瘤、衰老、遗传易感综合征等疾病发生直接相关。以早幼粒细胞白血病蛋白(promylocytic leukemia protein,PML)为核心分子构成的、与核基质相连的亚核多蛋白复合体——PML核体(PML nuclear body)既是DNA损伤的动态感受器,又是p53依赖和非依赖的检查点激活、损伤修复、凋亡诱导等细胞学反应的调控核心,在染色质重塑表观遗传调控、基因转录及转录后调控、蛋白共价修饰和活性调控等多个层面整合并协同调节DNA损伤反应。
The cell defense mechanisms of DNA damage response during long-term evolution include a series of cytological reactions such as transcriptional regulation, cycle regulation, injury repair, apoptosis and non-apoptotic death, which are the cornerstones of the maintenance of genome stability. The abnormal regulation and tumor, aging, genetic predisposition and other diseases are directly related. PML nuclear body, which is composed of promyelocytic leukemia protein (PML) as its core molecule and connected to the nuclear matrix, is not only a dynamic sensor of DNA damage, but also p53-dependent and independent checkpoint activation, injury repair, apoptosis induction and other cytological control of the core, in chromatin remodeling epigenetic regulation, gene transcription and post-transcriptional regulation, covalent modification and activity of protein control and more One level integrates and synergistically regulates DNA damage response.