Normal human chromosomes have long G-rich telomeric overhangs at one end

Woodring E. Wright, Valerie M. Tesmer, Kenneth E. Huffman, Stephen D. Levene, Jerry W. Shay

Research output: Contribution to journalArticle

523 Scopus citations

Abstract

Telomeres protect the ends of linear chromosomes from degradation and abnormal recombination events, and in vertebrates may be important in cellular senescence and cancer. However, very little is known about the structure of human telomeres. In this report we purify telomeres and analyze their termini. We show that following replication the daughter telomeres have different terminal overhangs in normal diploid telomerase-negative human fibroblasts. Electron microscopy of those telomeres that have long overhangs yields 200 ± 75 nucleotides of single-stranded DNA. This overhang is four times greater than the amount of telomere shortening per division found in these cells. These results are consistent with models of telomere replication in which leading-strand synthesis generates a blunt end while lagging-strand synthesis produces a long G-rich 3' overhang, and suggest that variations in lagging-strand synthesis may regulate the rate of telomere shortening in normal diploid human cells. Our results do not exclude the possibility that nuclease processing events following leading strand synthesis result in short overhangs on one end.

Original languageEnglish (US)
Pages (from-to)2801-2809
Number of pages9
JournalGenes and Development
Volume11
Issue number21
DOIs
StatePublished - Nov 1 1997

Keywords

  • Aging
  • Cellular senescence
  • Chromosome structure
  • DNA replication
  • Telomeres

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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