Integrator facilitates RNAPII removal to prevent transcription-replication collisions and genome instability.
Integrator complex
MCM complex
R-loop
RNA polymerase II
RNAPII
TRCs
fork reversal
genome stability
replication stress
replicative helicase
transcription-replication conflicts
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
06 Jul 2023
06 Jul 2023
Historique:
received:
16
02
2023
revised:
17
04
2023
accepted:
10
05
2023
pmc-release:
06
07
2024
medline:
10
7
2023
pubmed:
10
6
2023
entrez:
9
6
2023
Statut:
ppublish
Résumé
DNA replication preferentially initiates close to active transcription start sites (TSSs) in the human genome. Transcription proceeds discontinuously with an accumulation of RNA polymerase II (RNAPII) in a paused state near the TSS. Consequently, replication forks inevitably encounter paused RNAPII soon after replication initiates. Hence, dedicated machinery may be needed to remove RNAPII and facilitate unperturbed fork progression. In this study, we discovered that Integrator, a transcription termination machinery involved in the processing of RNAPII transcripts, interacts with the replicative helicase at active forks and promotes the removal of RNAPII from the path of the replication fork. Integrator-deficient cells have impaired replication fork progression and accumulate hallmarks of genome instability including chromosome breaks and micronuclei. The Integrator complex resolves co-directional transcription-replication conflicts to facilitate faithful DNA replication.
Identifiants
pubmed: 37295432
pii: S1097-2765(23)00371-4
doi: 10.1016/j.molcel.2023.05.015
pmc: PMC10330747
mid: NIHMS1903126
pii:
doi:
Substances chimiques
RNA Polymerase II
EC 2.7.7.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2357-2366.e8Subventions
Organisme : NIEHS NIH HHS
ID : K99 ES034058
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239161
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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