Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.
DNA damage
DNA replication
G2/M DNA synthesis
RNA polymerase II transcription
Replication origins
transcription-associated genome instability
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 02 2021
16 02 2021
Historique:
received:
21
11
2019
revised:
09
11
2020
accepted:
26
01
2021
entrez:
17
2
2021
pubmed:
18
2
2021
medline:
3
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33596418
pii: S2211-1247(21)00072-3
doi: 10.1016/j.celrep.2021.108759
pmc: PMC7900609
pii:
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108759Subventions
Organisme : Medical Research Council
ID : MC_PC_14123
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P009085/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202115/Z/16/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S016155/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C17422/A25154
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009882/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K01076X/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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