PTOP interacts with POT1 and regulates its localization to telomeres

Nat Cell Biol. 2004 Jul;6(7):673-80. doi: 10.1038/ncb1142. Epub 2004 Jun 6.

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). In human cells, the loading of POT1 to telomeric ssDNA controls telomerase-mediated telomere elongation. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Cellular Senescence / genetics
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • Dimerization
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • RNA Interference / physiology
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / isolation & purification
  • Telomere-Binding Proteins / metabolism*

Substances

  • ACD protein, human
  • DNA, Complementary
  • DNA, Single-Stranded
  • POT1 protein, human
  • TINF2 protein, human
  • Telomere-Binding Proteins

Associated data

  • GENBANK/AY502940