Treacle and TOPBP1 control replication stress response in the nucleolus.

Tytuł:: Treacle and TOPBP1 control replication stress response in the nucleolus.
Autorzy:: Velichko AK; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
Ovsyannikova N; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Petrova NV; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Luzhin AV; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Vorobjeva M; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Gavrikov AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, Russia.
Mishin AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, Russia.
Kireev II; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.; V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Moscow, Russia.
Razin SV; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Kantidze OL; Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Źródło:: The Journal of cell biology [J Cell Biol] 2021 Aug 02; Vol. 220 (8). Date of Electronic Publication: 2021 Jun 08.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: New York : Rockefeller University Press
MeSH Terms:: DNA Damage*
DNA Replication*
Carrier Proteins/*metabolism
Cell Nucleolus/*metabolism
DNA, Ribosomal/*biosynthesis
DNA-Binding Proteins/*metabolism
Nuclear Proteins/*metabolism
Phosphoproteins/*metabolism
Aphidicolin/pharmacology ; Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Carrier Proteins/genetics ; Cell Nucleolus/drug effects ; Cell Nucleolus/genetics ; DNA, Ribosomal/genetics ; 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
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Substance Nomenclature:: 0 (Carrier Proteins)
0 (DNA, Ribosomal)
0 (DNA-Binding Proteins)
0 (Nuclear Proteins)
0 (Phosphoproteins)
0 (TCOF1 protein, human)
0 (TOPBP1 protein, human)
38966-21-1 (Aphidicolin)
EC 2.7.11.1 (ATR protein, human)
EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
X6Q56QN5QC (Hydroxyurea)
Entry Date(s):: Date Created: 20210608 Date Completed: 20211018 Latest Revision: 20220204
Update Code:: 20240104
PubMed Central ID:: PMC8190600
DOI:: 10.1083/jcb.202008085
PMID:: 34100862
: Czasopismo naukowe

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.
(© 2021 Velichko et al.)

Comment in: Nat Rev Mol Cell Biol. 2021 Aug;22(8):507. (PMID: 34172952)

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