Embryonic genome instability upon DNA replication timing program emergence.

ABSTRACT: Faithful DNA replication is essential for genome integrity^1-4. Under-replicated DNA leads to defects in chromosome segregation, which are common during embryogenesis^5-8. However, the regulation of DNA replication remains poorly understood in early mammalian embryos. Here we constructed a single-cell genome-wide DNA replication atlas of pre-implantation mouse embryos and identified an abrupt replication program switch accompanied by a transient period of genomic instability. In 1- and 2-cell embryos, we observed the complete absence of a replication timing program, and the entire genome replicated gradually and uniformly using extremely slow-moving replication forks. In 4-cell embryos, a somatic-cell-like replication timing program commenced abruptly. However, the fork

SUBMITTER: Takahashi S 

PROVIDER: S-EPMC11410655 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature