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The multiple facets of the intra-S checkpoint.

机译:S内部检查点的多个方面。

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摘要

In response to hydroxyurea treatment or DNA damage the total rate of DNA replication per cell is reduced. This reduction may be due to physical hindrance of the replication forks or to active, checkpoint-dependent processes. Here we review current knowledge about how and to what extent the intra-S checkpoint affects DNA replication. We discuss evidence that some checkpoint proteins are active even in a normal S phase and we suggest a model that resolves the apparent contradiction between different views on checkpoint-dependent slowing of the rate of DNA replication: does the intra-S checkpoint repress or delay the initiation of all origins or late replication origins only, and to what extent does it inhibit fork progression. Finally, the new model is discussed in the context of cancer development.
机译:响应羟基脲处理或DNA损伤,每个细胞DNA复制的总速率降低。这种减少可能是由于复制叉的物理障碍或由于活动,依赖检查点的进程而引起的。在这里,我们回顾了有关S内检查点如何以及在多大程度上影响DNA复制的知识。我们讨论了一些检查点蛋白甚至在正常S期仍具有活性的证据,并提出了一种模型,该模型可以解决不同检查点之间依赖于检查点的DNA复制速率减慢的明显矛盾:S内检查点是否抑制或延迟了仅起源于所有起源或晚期复制起源,并且在多大程度上抑制了叉子的发展。最后,在癌症发展的背景下讨论了新模型。

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