Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication

Autor:	Raghav, Chawla, Sophie, Redon, Christina, Raftopoulou, Harry, Wischnewski, Sarantis, Gagos, Claus M, Azzalin
Rok vydání:	2011
Předmět:	Cell Nucleus Proteomics Proteome Cell Cycle Telomere-Binding Proteins Telomere Models Biological Shelterin Complex Article Cell Line Trans-Activators Humans Telomerase RNA Helicases HeLa Cells
Zdroj:	The EMBO journal The EMBO Journal
DOI:	10.1038/emboj.2011.280
Popis:	Eukaryotic up-frameshift 1 (UPF1) is a nucleic acid-dependent ATPase and 5'-to-3' helicase, best characterized for its roles in cytoplasmic RNA quality control. We previously demonstrated that human UPF1 binds to telomeres in vivo and its depletion leads to telomere instability. Here, we show that UPF1 is present at telomeres at least during S and G2/M phases and that UPF1 association with telomeres is stimulated by the phosphoinositide 3-kinase (PI3K)-related protein kinase ataxia telangiectasia mutated and Rad3-related (ATR) and by telomere elongation. UPF1 physically interacts with the telomeric factor TPP1 and with telomerase. Akin to UPF1 binding to telomeres, this latter interaction is mediated by ATR. Moreover, the ATPase activity of UPF1 is required to prevent the telomeric defects observed upon UPF1 depletion, and these defects stem predominantly from inefficient telomere leading-strand replication. Our results portray a scenario where UPF1 orchestrates crucial aspects of telomere biology, including telomere replication and telomere length homeostasis.
Databáze:	OpenAIRE
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