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Phase 'separating' 53BP1 from DSB repair

RESEARCH HIGHLIGHTS

Phase 'separating' 53BP1 from DSB repair

Youwei Zhang
Genes & Diseases第10卷, 第1期pp.1-3纸质出版 2023-01-01在线发表 2022-05-14
118400

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. 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, HP1a, b and g, 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 HP1b and HP1g have both genesilencing and gene-activating roles, probably due to the slight structural difference.

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