Treacle and TOPBP1 control replication stress response in the nucleolus

Velichko, A.; Ovsiannikova, N.; Petrova, N.; Luzhin, A.; Panyavina, M.; Gavrikov, A.; Mishin, A.; Kireev, I.; Razin, S.; Kantidze, O.

Авторы: Velichko Artem, Ovsiannikova Natalia, Petrova Nadezhda, Luzhin Artem, Panyavina Maria, Gavrikov Alexey, Mishin Alexander, Kireev Igor, Razin Sergey, Kantidze Omar
Журнал: Journal of Cell Biology
Том: 220
Номер: 8
Год издания: 2021
Издательство: Rockefeller University Press
Местоположение издательства: United States
DOI: 10.1083/jcb.202008085
Аннотация: 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
Добавил в систему: Разин Сергей Владимирович

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Treacle and TOPBP1 control replication stress response in the nucleolusстатья

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