Role of HP1β during spermatogenesis and DNA replication.

IF 2.5 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chromosoma Pub Date : 2020-12-01 Epub Date: 2020-07-10 DOI:10.1007/s00412-020-00739-4

Vijay Charaka, Anjana Tiwari, Raj K Pandita, Clayton R Hunt, Tej K Pandita

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引用次数: 4

Abstract

Heterochromatin protein 1β (HP1β), encoded by the Cbx1 gene, has been functionally linked to chromatin condensation, transcriptional regulation, and DNA damage repair. Here we report that testis-specific Cbx1 conditional knockout (Cbx1 cKO) impairs male germ cell development in mice. Depletion of HP1β negatively affected sperm maturation and increased seminiferous tubule degeneration in Cbx1 cKO mice. In addition, the spermatogonia have elevated γ-H2AX foci levels as do Cbx1 deficient mouse embryonic fibroblasts (MEFs) as compared to wild-type (WT) control MEFs. The increase in γ-H2AX foci in proliferating Cbx1 cKO cells indicates defective replication-dependent DNA damage repair. Depletion or loss of HP1β from human cells and MEFs increased DNA replication fork stalling and firing of new origins of replication, indicating defective DNA synthesis. Taken together, these results suggest that loss of HP1β in proliferating cells leads to DNA replication defects with associated DNA damage that impact spermatogenesis.

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HP1β在精子发生和DNA复制中的作用。

由Cbx1基因编码的异染色质蛋白1β (HP1β)在功能上与染色质凝聚、转录调控和DNA损伤修复有关。在这里，我们报道了睾丸特异性Cbx1条件敲除(Cbx1 cKO)会损害小鼠的雄性生殖细胞发育。在Cbx1 cKO小鼠中，HP1β的缺失对精子成熟和精小管变性有负面影响。此外，与野生型(WT)对照mef相比，精原细胞中Cbx1缺陷小鼠胚胎成纤维细胞(mef)的γ-H2AX病灶水平升高。增殖的Cbx1 cKO细胞中γ-H2AX灶的增加表明复制依赖性DNA损伤修复存在缺陷。人类细胞和mef中HP1β的消耗或缺失增加了DNA复制叉的停滞和新复制起点的启动，表明DNA合成有缺陷。综上所述，这些结果表明增殖细胞中HP1β的缺失导致DNA复制缺陷和相关的DNA损伤，从而影响精子发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chromosoma 生物-生化与分子生物学

CiteScore

3.30

自引率

6.20%

发文量

审稿时长

1 months

期刊介绍： Chromosoma publishes research and review articles on the functional organization of the eukaryotic cell nucleus, with a particular emphasis on the structure and dynamics of chromatin and chromosomes; the expression and replication of genomes; genome organization and evolution; the segregation of genomes during meiosis and mitosis; the function and dynamics of subnuclear compartments; the nuclear envelope and nucleocytoplasmic interactions, and more. The scope of Chromosoma encompasses genetic, biophysical, molecular and cell biological studies. Average time from receipt of contributions to first decision: 22 days Publishes research and review articles on the functional organization of the eukaryotic cell nucleus Topics include structure and dynamics of chromatin and chromosomes; the expression and replication of genomes; genome organization and evolution; the segregation of genomes during meiosis and mitosis and more Encompasses genetic, biophysical, molecular and cell biological studies.