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对复制体的实时追踪揭示了新月柄杆菌中复制延伸速率的营养物依赖性调控。

Live tracking of replisomes reveals nutrient-dependent regulation of replication elongation rates in Caulobacter crescentus.

作者信息

Adhikashreni Inchara S, Joseph Asha Mary, Phadke Sneha, Badrinarayanan Anjana

机构信息

National Centre for Biological Sciences (TIFR), Bengaluru 560065, India.

National Centre for Biological Sciences (TIFR), Bengaluru 560065, India.

出版信息

Curr Biol. 2025 Apr 21;35(8):1816-1827.e3. doi: 10.1016/j.cub.2025.03.009. Epub 2025 Mar 31.

Abstract

In bacteria, commitment to genome replication (initiation) is intricately linked to nutrient availability. Whether growth conditions affect other stages of replication beyond initiation remains to be systematically studied. To address this, we assess the replication dynamics of Caulobacter crescentus, a bacterium that undergoes only a single round of replication per cell cycle, by tracking the replisome across various growth phases and nutrient conditions. We find that the replication elongation rates slow down as cells transition from exponential (high-nutrient) to stationary (low-nutrient) phase, and this contributes significantly to the overall cell-cycle delay. Although elongation rates are correlated with growth rates, both properties are differentially influenced by nutrient status. This slowdown in replication progression is reversed via supplementation with dNTPs and is not associated with increased mutagenesis or upregulation of the DNA damage responses. We conclude that growth conditions not only dictate the commitment to replication but also the rates of genome duplication. Such regulation appears to be distinct from stress-induced replication slowdown and likely serves as an adaptive mechanism to cope with fluctuations in nutrient availability in the environment.

摘要

在细菌中,基因组复制的起始与营养物质的可利用性密切相关。生长条件是否会影响起始之外的其他复制阶段仍有待系统研究。为了解决这个问题,我们通过追踪新月柄杆菌在不同生长阶段和营养条件下的复制体,来评估其复制动态。新月柄杆菌每个细胞周期仅进行一轮复制。我们发现,当细胞从指数期(高营养)过渡到稳定期(低营养)时,复制延伸速率会减慢,这对整体细胞周期延迟有显著影响。尽管延伸速率与生长速率相关,但这两个特性受营养状态的影响不同。通过补充脱氧核苷酸三磷酸(dNTPs)可逆转复制进程的这种减慢,且这与诱变增加或DNA损伤反应上调无关。我们得出结论,生长条件不仅决定复制的起始,还决定基因组复制的速率。这种调控似乎不同于应激诱导的复制减慢,可能是一种应对环境中营养物质可利用性波动的适应性机制。

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