PTOP interacts with POT1 and regulates its localization to telomeres (original) (raw)

Nature Cell Biology volume 6, pages 673–680 (2004)Cite this article

Abstract

Telomere maintenance has been implicated in cancer and ageing, and requires cooperation between a multitude of telomeric factors, including telomerase, TRF1, TRF2, RAP1, TIN2, Tankyrase, PINX1 and POT1 (refs 1–12). POT1 belongs to a family of oligonucleotide-binding (OB)-fold-containing proteins that include Oxytricha nova TEBP, Cdc13, and spPot1, which specifically recognize telomeric single-stranded DNA (ssDNA)10,13,14,15,16,17,18,19. In human cells, the loading of POT1 to telomeric ssDNA controls telomerase-mediated telomere elongation12. Surprisingly, a human POT1 mutant lacking an OB fold is still recruited to telomeres. However, the exact mechanism by which this recruitment occurs remains unclear. Here we identify a novel telomere protein, PTOP, which interacts with both POT1 and TIN2. PTOP binds to the carboxyl terminus of POT1 and recruits it to telomeres. Inhibition of PTOP by RNA interference (RNAi) or disruption of the PTOP–POT1 interaction hindered the localization of POT1 to telomeres. Furthermore, expression of the respective interaction domains on PTOP and POT1 alone extended telomere length in human cells. Therefore, PTOP heterodimerizes with POT1 and regulates POT1 telomeric recruitment and telomere length.

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Acknowledgements

We would like to thank T. de Lange for kindly providing the POT1 antibody. We would also like to thank M. Rodriguez for help with the peptide array analysis. This work was supported by awards to Z.S. from National Institutes of Health, the Department of Defence, and the Welch Foundation.

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Authors and Affiliations

  1. Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, 77030, TX, USA
    Dan Liu, Amin Safari, Matthew S O'Connor, Doug W. Chan, Andrew Laegeler, Jun Qin & Zhou Songyang

Authors

  1. Dan Liu
  2. Amin Safari
  3. Matthew S O'Connor
  4. Doug W. Chan
  5. Andrew Laegeler
  6. Jun Qin
  7. Zhou Songyang

Corresponding author

Correspondence toZhou Songyang.

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The authors declare no competing financial interests.

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Liu, D., Safari, A., O'Connor, M. et al. PTOP interacts with POT1 and regulates its localization to telomeres.Nat Cell Biol 6, 673–680 (2004). https://doi.org/10.1038/ncb1142

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