Telomere protection by mammalian Pot1 requires interaction with Tpp1.
The shelterin complex at mammalian telomeres contains the single-stranded DNA-binding protein Pot1, which regulates telomere length and protects chromosome ends. Pot1 binds Tpp1, the shelterin component that connects Pot1 to the duplex telomeric DNA-binding proteins Trf1 and Trf2. Control of telomere length requires that Pot1 binds Tpp1 as well as the single-stranded telomeric DNA, but it is not known whether the protective function of Pot1 depends on Tpp1. Alternatively, Pot1 might function similarly to the Pot1-like proteins of budding and fission yeast, which have no known Tpp1-like connection to the duplex telomeric DNA. Using mutant mouse cells with diminished Tpp1 levels, RNA interference directed to mouse Tpp1 and Pot1, and complementation of mouse Pot1 knockout cells with human and mouse Pot1 variants, we show here that Tpp1 is required for the protective function of mammalian Pot1 proteins.
Hockemeyer
Dirk
D
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Palm
Wilhelm
W
Else
Tobias
T
Daniels
Jan-Peter
JP
Takai
Kaori K
KK
Ye
Jeffrey Z-S
JZ
Keegan
Catherine E
CE
de Lange
Titia
T
Hammer
Gary D
GD
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D034622:RNA Interference; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D035341:Telomeric Repeat Binding Protein 2
C495876:ACD protein, human; C544060:Acd protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C440849:POT1 protein, human; C507326:POT1 protein, mouse; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2