Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection

Nat Struct Mol Biol. 2004 Dec;11(12):1223-9. doi: 10.1038/nsmb867. Epub 2004 Nov 21.


The POT1 (protection of telomeres 1) protein binds the single-stranded overhang at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome end-protection in the fission yeast Schizosaccharomyces pombe, and it is involved in regulation of telomere length in human cells. Here, we report the crystal structure at a resolution of 1.73 A of the N-terminal half of human POT1 (hPOT1) protein bound to a telomeric single-stranded DNA (ssDNA) decamer, TTAGGGTTAG, the minimum tight-binding sequence indicated by in vitro binding assays. The structure reveals that hPOT1 contains two oligonucleotide/ oligosaccharide-binding (OB) folds; the N-terminal OB fold binds the first six nucleotides, resembling the structure of the S. pombe Pot1pN-ssDNA complex, whereas the second OB fold binds and protects the 3' end of the ssDNA. These results provide an atomic-resolution model for chromosome end-capping.

Publication types

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

MeSH terms

  • Base Sequence
  • Crystallography, X-Ray
  • DNA, Single-Stranded / chemistry*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • Humans
  • Models, Biological
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Structure, Tertiary
  • Schizosaccharomyces pombe Proteins
  • Shelterin Complex
  • Telomerase / metabolism
  • Telomere / chemistry
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / chemistry*
  • Telomere-Binding Proteins / metabolism*


  • DNA, Single-Stranded
  • POT1 protein, human
  • Schizosaccharomyces pombe Proteins
  • Shelterin Complex
  • Telomere-Binding Proteins
  • pot1 protein, S pombe
  • Telomerase

Associated data

  • PDB/1XJV