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The impact of replication stress on replication dynamics and DNA damage in vertebrate cells
Nature Reviews Genetics ( IF 42.7 ) Pub Date : 2017-07-17 00:00:00 , DOI: 10.1038/nrg.2017.46
Hervé Técher , Stéphane Koundrioukoff , Alain Nicolas , Michelle Debatisse

The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression. Recent studies have yielded insights into sequence-dependent and sequence-independent sources of endogenous replication stress. These stresses result in nuclease-induced DNA damage, checkpoint activation and genome-wide replication fork slowing. Several hypotheses have been proposed to account for the mechanisms involved in this complex response. Recent results have shown that the slowing of the replication forks most commonly results from DNA precursor starvation. By concomitantly increasing the density of replication initiation, the cell elicits an efficient compensatory strategy to avoid mitotic anomalies and the inheritance of damage over cell generations.

中文翻译:

复制应力对脊椎动物细胞复制动力学和DNA损伤的影响

复制压力和S期检查点之间的相互作用是基因组维持的关键决定因素,并且对人类疾病(尤其是肿瘤的发生和发展)具有重大影响。最近的研究对内源性复制应激的序列依赖性和序列依赖性来源产生了深刻见解。这些压力导致核酸酶诱导的DNA损伤,检查点激活和全基因组复制叉变慢。已经提出了几种假设来解释这种复杂反应所涉及的机制。最近的结果表明,复制叉的减慢最常见是由DNA前体饥饿引起的。通过同时增加复制起始的密度,
更新日期:2017-08-17
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