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在早期胚胎 DNA 复制周期中保持基因组完整性。

Preserving Genome Integrity During the Early Embryonic DNA Replication Cycles.

机构信息

Laboratoire Surveillance et Stabilité du Génome, Institut de Génétique Humaine, UMR9002, CNRS, Université de Montpellier, 34090 Montpellier, France.

Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA.

出版信息

Genes (Basel). 2019 May 24;10(5):398. doi: 10.3390/genes10050398.

Abstract

During the very early stages of embryonic development chromosome replication occurs under rather challenging conditions, including a very short cell cycle, absence of transcription, a relaxed DNA damage response and, in certain animal species, a highly contracted S-phase. This raises the puzzling question of how the genome can be faithfully replicated in such a peculiar metabolic context. Recent studies have provided new insights into this issue, and unveiled that embryos are prone to accumulate genetic and genomic alterations, most likely due to restricted cellular functions, in particular reduced DNA synthesis quality control. These findings may explain the low rate of successful development in mammals and the occurrence of diseases, such as abnormal developmental features and cancer. In this review, we will discuss recent findings in this field and put forward perspectives to further study this fascinating question.

摘要

在胚胎发育的早期阶段,染色体复制发生在相当具有挑战性的条件下,包括非常短的细胞周期、转录缺失、松弛的 DNA 损伤反应,以及在某些动物物种中,高度收缩的 S 期。这就提出了一个令人费解的问题,即在如此特殊的代谢环境下,基因组如何能被忠实复制。最近的研究为这个问题提供了新的见解,并揭示了胚胎容易积累遗传和基因组改变,这很可能是由于细胞功能受限,特别是 DNA 合成质量控制降低所致。这些发现可以解释哺乳动物发育成功率低和疾病(如发育异常和癌症)的发生。在这篇综述中,我们将讨论该领域的最新发现,并提出进一步研究这一迷人问题的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb48/6563053/e45ebd867210/genes-10-00398-g001.jpg

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