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Embryonic genome instability upon DNA replication timing program emergence

ABSTRACT: Embryonic genome instability upon DNA replication timing program emergence

PROVIDER: PRJNA939700 | ENA |

REPOSITORIES: ENA

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Embryonic genome instability upon DNA replication timing program emergence

Project description:Embryonic genome instability upon DNA replication timing program emergence

| PRJNA1075049 | ENA

Embryonic genome instability upon DNA replication timing program emergence

Project description:Faithful DNA replication is essential for genome integrity. Under-replicated DNA leads to chromosome segregation defects, which are reportedly common during embryogenesis. However, DNA replication regulation remains poorly understood in early mammalian embryos. Here, we constructed a single-cell genome-wide DNA replication atlas of pre-implantation mouse embryos and discovered 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 (RT) program, and the entire genome replicated gradually and uniformly using extremely slow-moving forks. In 4-cell embryos, a somatic-cell-like RT program commenced abruptly. However, the fork speed was still slow, S-phase was extended, and SLX4 DNA repair foci increased during G2/M, which was followed by a transient increase in chromosome segregation errors. Importantly, live imaging captured longer S-phase of error cells, and the breakpoints identified by single-cell genome sequencing were enriched in late-replicating regions. By the 8-cell stage, forks gained speed, S-phase was no longer extended, and chromosome aberrations disappeared. Thus, a transient period of genomic instability exists during normal mouse development, which is preceded by a fragile S-phase lacking the coordination between replisome-level regulation and megabase-scale RT regulation, implicating the importance of their coordination for genome integrity.

2024-06-24 | GSE226309 | GEO

Decoding the Replication Timing Program in Zebrafish: The Role of Rif1

Project description:Deregulated DNA replication is a major contributor to human developmental disorders and cancer, yet our understanding of how replication is coordinated with changes in transcription and chromatin structure is limited. Our lab has employed the zebrafish model to investigate the mechanisms driving changes in the replication timing program during development. Previous studies have identified changes in replication timing patterns from the onset of zygotic transcription through gastrulation in zebrafish embryos. The protein Rif1 is crucial for replication timing in a wide range of eukaryotes, yet its role in establishing the replication timing program and chromatin structure during early vertebrate development is not well understood. Using Rif1 mutant zebrafish and performing RNA sequencing and whole-genome replication timing analysis, we found that Rif1 mutants were viable but had a defect in female sex determination. Interestingly, Rif1 loss primarily affected DNA replication timing after gastrulation, while its impact on transcription was more pronounced during zygotic genome activation. Our results indicate that Rif1 has distinct roles in regulating DNA replication and transcription at different stages of development.

2023-08-15 | GSE225957 | GEO

Replication timing program in 6 human model cell lines

Project description:We present here the characterization of the replication timing program in 6 human cell lines : U2OS, RKO, 293T, HeLa, MRC5 and K562

2016-07-08 | GSE80029 | GEO

MRC1-Dependent Scaling of the Budding Yeast DNA Replication Timing Program

Project description:Fourteen yeast mutants with an extended S-phase were identified by a novel genome-wide screen. These mutants are associated with the DNA replication machinery, cell-cycle control and dNTP synthesis. We determined the genome-wide DNA replication timing profile of all these mutants as well as wild type, by FACS-sorting G1- and S-phase cells and co-hybridizing their DNA to Agilent genomic tiling arrays, in four repeats each. We find that MRC1 is required for scaling of the DNA replication timing program upon replication perturbation.

2010-03-04 | GSE17120 | GEO

Single-cell replication profiling reveals stochastic regulation of the mammalian replication-timing program

Project description:Single-cell replication profiling reveals stochastic regulation of the mammalian replication-timing program

| PRJNA396545 | ENA

The effect of ATR inhibition on the replication timing program

Project description:The effect of ATR inhibition on the replication timing program

| PRJNA760530 | ENA

The effect of ATR inhibition on the replication timing program

Project description:The effect of ATR inhibition on the replication timing program

| PRJNA542329 | ENA

The effect of WEE1 inhibition on the replication timing program

Project description:The effect of WEE1 inhibition on the replication timing program

| PRJNA577964 | ENA

Embryonic genome instability upon DNA replication timing program emergence

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-24 | GSE255458 | GEO

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