Recognition of a chromosome truncation site associated with alpha-thalassaemia by human telomerase

Nature. 1991 Oct 3;353(6343):454-6. doi: 10.1038/353454a0.


Telomeres define the ends of chromosomes; they consist of short tandemly repeated DNA sequences loosely conserved in eukaryotes (G1-8(T/A)1-4). Telomerase is a ribonucleoprotein which, in vitro, recognizes a single-stranded G-rich telomere primer and adds multiple telomeric repeats to its 3' end by using a template in the RNA moiety. In conjunction with other components, telomerase may balance the loss of telomeric repeats due to DNA replication. Another role of telomerase may be the de novo formation of telomeres. In eukaryotes like Tetrahymena, this process is an integral part of the formation of macronuclear chromosomes. In other eukaryotes this process stabilizes broken chromosomes. A case of human alpha-thalassaemia is caused by a truncation of chromosome 16 that has been healed by the addition of telomeric repeats (TTAGGG)n. Using an in vitro assay, I show here that human telomerase correctly recognizes the chromosome 16 breakpoint sequence and adds (TTAGGG)n repeats. The DNA sequence requirements are minimal and seem to define two modes of DNA recognition by telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition
  • Base Sequence
  • Chromosomes, Human, Pair 16 / metabolism*
  • DNA Nucleotidylexotransferase / metabolism*
  • DNA, Single-Stranded / metabolism
  • Guanosine
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Repetitive Sequences, Nucleic Acid
  • Templates, Genetic
  • Thalassemia / genetics*


  • DNA, Single-Stranded
  • Guanosine
  • DNA Nucleotidylexotransferase