美国哥伦比亚大学Dieter Egli团队发现，复制压力损害人类胚胎的染色体分离和着床前发育。2022年7月19日，《细胞》杂志在线发表了这项成果。

Title: Replication stress impairs chromosome segregation and preimplantation development in human embryos

Author: Katherine L. Palmerola, Selma Amrane, Alejandro De Los Angeles, Shuangyi Xu, Ning Wang, Joao de Pinho, Michael V. Zuccaro, Angelo Taglialatela, Dashiell J. Massey, Jenna Turocy, Alex Robles, Anisa Subbiah, Bob Prosser, Rogerio Lobo, Alberto Ciccia, Amnon Koren, Timour Baslan, Dieter Egli

Issue&Volume: 2022-07-19

Abstract: Human cleavage-stage embryos frequently acquire chromosomal aneuploidies during mitosisdue to unknown mechanisms. Here, we show that S phase at the 1-cell stage shows replicationfork stalling, low fork speed, and DNA synthesis extending into G2 phase. DNA damagefoci consistent with collapsed replication forks, DSBs, and incomplete replicationform in G2 in an ATR- and MRE11-dependent manner, followed by spontaneous chromosomebreakage and segmental aneuploidies. Entry into mitosis with incomplete replicationresults in chromosome breakage, whole and segmental chromosome errors, micronucleation,chromosome fragmentation, and poor embryo quality. Sites of spontaneous chromosomebreakage are concordant with sites of DNA synthesis in G2 phase, locating to gene-poorregions with long neural genes, which are transcriptionally silent at this stage ofdevelopment. Thus, DNA replication stress in mammalian preimplantation embryos predisposesgene-poor regions to fragility, and in particular in the human embryo, to the formationof aneuploidies, impairing developmental potential.

DOI: 10.1016/j.cell.2022.06.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00780-2