Telomere-end processing: The terminal nucleotidesof human chromosomes

Agnel J. Sfeir, Weihang Chai, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Mammalian telomeres end in single-stranded, G-rich 3′ overhangs resulting from both the "end-replication problem" (the inability of DNA polymerase to replicate the very end of the telomeres) and postreplication processing. Telomeric G-rich overhangs are precisely defined in ciliates; the length and the terminal nucleotides are fixed. Human telomeres have very long overhangs that are heterogeneous in size (35-600 nt), indicating that their processing must differ in some respects from model organisms. We developed telomere-end ligation protocols that allowed us to identify the terminal nucleotides of both the C-rich and the G-rich telomere strands. Up to ∼80% of the C-rich strands terminate in CCAATC-5′, suggesting that after replication a nuclease with high specificity or constrained action acts on the C strand. In contrast, the G-terminal nucleotide was less precise than Tetrahymena and Euplotes but still had a bias that changed as a function of telomerase expression.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalMolecular cell
Volume18
Issue number1
DOIs
StatePublished - Apr 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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