GSE160831
G2/M DNA synthesis at transcription start sites because of RNA transcription persistence during DNA replication [REPLI-Seq async]
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. Overall design: Genome-wide DNA replication of BJ-hTERT by BrdU-seq, with cells sorted in 5 fractions based on their DNA content