Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse.
CMG
Replication fork stability
Replication stress
iPOND
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
31
12
2018
accepted:
20
06
2019
revised:
04
06
2019
pubmed:
13
7
2019
medline:
7
3
2020
entrez:
13
7
2019
Statut:
ppublish
Résumé
During S phase, replication forks can encounter several obstacles that lead to fork stalling, which if persistent might result in fork collapse. To avoid this collapse and to preserve the competence to restart, cells have developed mechanisms that maintain fork stability upon replication stress. In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain associated with chromatin upon acute hydroxyurea treatment, whereas replisome stability is lost upon a sustained replication stress that compromises the competence to restart.
Identifiants
pubmed: 31297568
doi: 10.1007/s00018-019-03206-1
pii: 10.1007/s00018-019-03206-1
doi:
Substances chimiques
DNA, Single-Stranded
0
Hydroxyurea
X6Q56QN5QC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
735-749Subventions
Organisme : Ministerio de Economía y Competitividad
ID : SAF2013-42742-R
Organisme : Ministerio de Economía y Competitividad
ID : SAF2016-76239-R
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