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首页> 外文期刊>Cell cycle >DNA replication in early S phase pauses near newly activated origins.
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DNA replication in early S phase pauses near newly activated origins.

机译：S期早期的DNA复制在新激活的起点附近暂停。

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摘要

During the S phase of the cell cycle, the entire genome is replicated. There is a high level of orderliness to this process through the temporally and topologically coordinated activation of many replication origins situated along chromosomes. We investigated the program of replication from origins initiating in early S phase by labeling synchronized normal human fibroblasts (NHF1) with nucleotide analogs for various pulse times and measuring labeled tracks in combed DNA fibers. Our analysis showed that replication forks progress 9-35 kilobases from newly initiated origins, followed by a pause in synthesis before replication resumes. Pausing was not observed near origins that initiated in the middle of S phase. No evidence for pausing near origins was found at the beginning of the S phase in glioblastoma T98G cells. Treatment with the S phase checkpoint inhibitor caffeine abrogated pausing in NHF1 cells in early S phase. This suggests that pausing may comprise a novel aspect of the intra-S phase checkpoint pathway or a related new early S checkpoint. Further, it is possible that the loss of this regulatory process in cancer cells such as T98G could be a contributing factor in the genetic instability that typifies cancers.
机译：在细胞周期的S期，整个基因组被复制。通过沿染色体排列的许多复制起点的时间和拓扑协调激活，此过程具有高度的有序性。我们通过用核苷酸类似物标记同步的正常人成纤维细胞（NHF1）各种脉冲时间并测量梳状DNA纤维中的标记轨迹，研究了从S期早期启动的起点复制程序。我们的分析表明，复制叉从新启动的起点开始前进9-35千个碱基，然后在复制恢复之前暂停合成。在S期中间开始的起点附近未观察到暂停。在胶质母细胞瘤T98G细胞的S期开始时，没有发现中止起源的证据。 S期检查点抑制剂咖啡因的治疗消除了S期早期NHF1细胞的暂停。这表明暂停可能包括S内阶段检查点途径或相关的新S早期检查点的新颖方面。此外，可能在癌细胞（如T98G）中失去这种调节过程可能是导致癌症的遗传不稳定性的一个重要因素。

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