染色体间区区室化核结构PML-NB在DNA损伤反应中的功能意义  

The role of inter-chromosomal domain compartmentalized nuclear structure PML-NB in DNA damage responses

作　　者：宋宜[1] 田宝磊[1] 郑晓飞[1] 孙志贤[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《生命的化学》2013年第3期245-249,共5页Chemistry of Life

摘　　要：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。DNA damage responses （DDR） cellular defense mechanism acts as a potent barrier for tumor initiation and progression, containing transcriptional regulation, cell cycle checkpoint activation, DNA damage repair, apoptotic and non-apoptotic cell death, which is the cornerstone of genome stability. Dysfunction of DDR signaling is associated with genomic instability diseases, such as tumor, senescence and complex diseases. The promyelocytic leukemia protein （PML） is the indispensable scaffold of PML nuclear bodies （PML-NBs）, which are matrix associated multi-protein subnuclear structures. Previous studies have showed that PML-NBs are dynamic sensor of DNA damage, and regulate a wide variety of biological processes, including chromatin remodeling, epigenetic modification, gene transcription and post-transcriptional RNA stability and translation, post-translational protein modification and location. PML-NBs function as pivotal hub of signal transduction and network coordination in p53-dependent and p53-independent checkpoint activation, damage repair and apoptosis induction in DNA damage responses （DDR）.

关 键 词：早幼粒细胞白血病蛋白 核体 DNA损伤反应 

分 类 号：R733.7[医药卫生—肿瘤]