Treacle and TOPBP1 control replication stress response in the nucleolus.
Aphidicolin
/ pharmacology
Ataxia Telangiectasia Mutated Proteins
/ genetics
Carrier Proteins
/ genetics
Cell Nucleolus
/ drug effects
DNA Damage
DNA Replication
DNA, Ribosomal
/ biosynthesis
DNA-Binding Proteins
/ genetics
Genomic Instability
HCT116 Cells
HeLa Cells
Humans
Hydroxyurea
/ pharmacology
Microscopy, Fluorescence
Nuclear Proteins
/ genetics
Phosphoproteins
/ genetics
Protein Binding
Protein Transport
Signal Transduction
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 08 2021
02 08 2021
Historique:
received:
16
08
2020
revised:
26
04
2021
accepted:
18
05
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Replication stress is one of the main sources of genome instability. Although the replication stress response in eukaryotic cells has been extensively studied, almost nothing is known about the replication stress response in nucleoli. Here, we demonstrate that initial replication stress-response factors, such as RPA, TOPBP1, and ATR, are recruited inside the nucleolus in response to drug-induced replication stress. The role of TOPBP1 goes beyond the typical replication stress response; it interacts with the low-complexity nucleolar protein Treacle (also referred to as TCOF1) and forms large Treacle-TOPBP1 foci inside the nucleolus. In response to replication stress, Treacle and TOPBP1 facilitate ATR signaling at stalled replication forks, reinforce ATR-mediated checkpoint activation inside the nucleolus, and promote the recruitment of downstream replication stress response proteins inside the nucleolus without forming nucleolar caps. Characterization of the Treacle-TOPBP1 interaction mode leads us to propose that these factors can form a molecular platform for efficient stress response in the nucleolus.
Identifiants
pubmed: 34100862
pii: 212262
doi: 10.1083/jcb.202008085
pmc: PMC8190600
pii:
doi:
Substances chimiques
Carrier Proteins
0
DNA, Ribosomal
0
DNA-Binding Proteins
0
Nuclear Proteins
0
Phosphoproteins
0
TCOF1 protein, human
0
TOPBP1 protein, human
0
Aphidicolin
38966-21-1
ATR protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Hydroxyurea
X6Q56QN5QC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 Velichko et al.
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