Phase 'separating' 53BP1 from DSB repair.
Phase 'separating' 53BP1 from DSB repair.
复制标题
将 53BP1 与 DSB 修复相“分离”。
DOI：
10.1016/j.gendis.2022.04.024
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发表时间：
2023
期刊：
影响因子：
6.8
通讯作者：
Zhang,Youwei
中科院分区：
文献类型：
--
作者：
Zhang,Youwei
真核染色体在细胞核中占据特定区域，这是基因组稳定性和功能的关键。基于时空组织和压实模式，真核细胞染色质可以被识别为在核内部具有转录活性和松散包装的常染色质，以及在核周边或核仁周围具有转录抑制和高度压实的异染色质（图1）。越来越多的证据表明，异染色质通过保持染色体完整性和抑制或限制重复DNA的转录，在维持基因组稳定性和功能方面起着关键作用。异染色质通常可分为组成型和兼性型。组成型异染色质通常存在于重复的卫星DNA区域，如着丝粒周围和端粒。另一方面，兼性异染色质富含重复转座子，并且可以失去其浓缩结构，并在特定的发育或环境条件下变得转录活性。组成型异染色质的标志是组蛋白H3（通常称为H3 K9 me 3）的第9个赖氨酸残基处的三甲基化，其由“书写者”、杂色抑制因子3-9同源物1/2（SUV 39 H1/2）进行，并且将由“阅读者”、异染色质蛋白1（HP 1）识别。人类HP 1有三种旁系同源物HP 1 α、β和γ，它们分别由三种不同的基因编码，即染色体盒同源物5（Cbx 5）、Cbx 1和Cbx 3。HP 1 α通常与组成型异染色质相关，而HP 1 β和HP 1 γ可能由于结构上的微小差异，同时具有基因沉默和基因激活的作用。
Eukaryotic chromosomes occupy specific territories in the nucleus, which is key for genome stability and function. Based on the spatiotemporal organization and compaction pattern, eukaryotic chromatins can be recognized as transcriptionally active and loosely packed euchromatin in the nuclear interior and transcriptionally repressive and highly compacted heterochromatin at the nuclear periphery or around nucleoli (Fig. 1). Mounting evidence suggests that heterochromatin plays a critical role in maintaining genome stability and function by preserving the chromosome integrity and repressing or limiting transcription of repetitive DNA. Heterochromatin can be generally subcategorized into constitutive and facultative types. Constitutive heterochromatin is usually found at repetitive satellite DNA regions such as those at peri-centromeres and telomeres. On the other hand, facultative heterochromatin is rich in repetitive transposons and can lose its condensed structure and become transcriptionally active under specific developmental or environmental conditions. A hallmark of constitutive heterochromatin is tri-methylation at the 9th lysine residue of the histone protein H3 (commonly known as H3K9me3), which is carried out by the ‘writer’, suppressor of variegation 3–9 homolog 1/2 (SUV39H1/2), and will be recognized by the ‘reader’, heterochromatin protein 1 (HP1). Human HP1 has three paralogues, HP1α, β and γ, which are encoded by three different genes, chromobox homolog 5 (Cbx5), Cbx1, and Cbx3, respectively. It seems that HP1α is commonly associated with constitutive heterochromatin, whereas HP1β and HP1γ have both gene-silencing and gene-activating roles, probably due to the slight structural difference.