Embryonic stem cells maintain high origin activity and slow forks to coordinate replication with cell cycle progression.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-01 Epub Date: 2024-07-25 DOI:10.1038/s44319-024-00207-5

Kiminori Kurashima, Yasunao Kamikawa, Tomomi Tsubouchi

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引用次数: 0

Abstract

Embryonic stem (ES) cells are pluripotent stem cells that can produce all cell types of an organism. ES cells proliferate rapidly and are thought to experience high levels of intrinsic replication stress. Here, by investigating replication fork dynamics in substages of S phase, we show that mammalian pluripotent stem cells maintain a slow fork speed and high active origin density throughout the S phase, with little sign of fork pausing. In contrast, the fork speed of non-pluripotent cells is slow at the beginning of S phase, accompanied by increased fork pausing, but thereafter fork pausing rates decline and fork speed rates accelerate in an ATR-dependent manner. Thus, replication fork dynamics within the S phase are distinct between ES and non-ES cells. Nucleoside addition can accelerate fork speed and reduce origin density. However, this causes miscoordination between the completion of DNA replication and cell cycle progression, leading to genome instability. Our study indicates that fork slowing in the pluripotent stem cells is an integral aspect of DNA replication.

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胚胎干细胞保持高起源活性和慢叉，以协调复制和细胞周期进展。

胚胎干细胞（ES）是多能干细胞，可产生生物体的所有细胞类型。ES细胞增殖迅速，被认为经历了高水平的内在复制压力。在这里，我们通过研究S期子阶段的复制叉动态，表明哺乳动物多能干细胞在整个S期保持缓慢的复制叉速度和较高的活性起源密度，几乎没有复制叉暂停的迹象。相反，非多能细胞的分叉速度在S期开始时很慢，伴随着分叉暂停的增加，但此后分叉暂停率下降，分叉速度以依赖ATR的方式加快。因此，ES细胞和非ES细胞在S期的复制叉动态是不同的。添加核苷可加快分叉速度并降低起源密度。然而，这会造成DNA复制完成与细胞周期进展之间的不协调，从而导致基因组不稳定。我们的研究表明，多能干细胞中的分叉速度减慢是DNA复制不可或缺的一个方面。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.