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G2/M DNA synthesis at transcription start sites because of RNA transcription persistence during DNA replication

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136294 | GEO | 2021/02/17

REPOSITORIES: GEO

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Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.

Project description:As transcription and replication use DNA as substrate, conflicts between transcription and replication can occur, leading to genome instability with direct consequences for human health. To determine how the two processes are coordinated throughout S phase, we characterize both processes together at high resolution. We find that transcription occurs during DNA replication, with transcription start sites (TSSs) not fully replicated along with surrounding regions and remaining under-replicated until late in the cell cycle. TSSs undergo completion of DNA replication specifically when cells enter mitosis, when RNA polymerase II is removed. Intriguingly, G2/M DNA synthesis occurs at high frequency in unperturbed cell culture, but it is not associated with increased DNA damage and is fundamentally separated from mitotic DNA synthesis. TSSs duplicated in G2/M are characterized by a series of specific features, including high levels of antisense transcription, making them difficult to duplicate during S phase.

| S-EPMC7900609 | biostudies-literature

G2/M DNA synthesis at transcription start sites because of RNA transcription persistence during DNA replication [ChIP-seq]

Project description:RNA transcription and DNA replication both use DNA as a substrate, that however can be engaged only by one of them at any given time. Consequently, conflicts between transcription and replication significantly affect genome stability and human health. To understand the reciprocal interplay between transcription and replication in human cells, we performed a genome-wide analysis of the two processes throughout S-phase. We found that transcription persists during replication, with direct consequences for replication progression through genes and sites of DNA damage. Importantly however, we also found that transcription start sites will not be replicated together with the surrounding regions, and remain under-replicated throughout S-phase. DNA synthesis across transcription start sites occurs specifically when cells enter mitosis, because the RNA Polymerase II is removed at that point from the majority of the genes. Intriguingly, this G2/M DNA synthesis is not associated with increased DNA damage and occurs at very high frequency.

2021-02-17 | GSE136291 | GEO

G2/M DNA synthesis at transcription start sites because of RNA transcription persistence during DNA replication [BrdU-Seq]

2021-02-17 | GSE136288 | GEO

G2/M DNA synthesis at transcription start sites because of RNA transcription persistence during DNA replication [G2M BrdU-Seq]

2021-02-17 | GSE136293 | GEO