A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint

Rhett J. Michelson, Saul Rosenstein, Ted Weinert

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Telomeres are complex structures that serve to protect chromosome ends. Here we provide evidence that in Saccharomyces cerevisiae telomeres may contain an anticheckpoint activity that prevents chromosome ends from signaling cell cycle arrest. We found that an internal tract of telomeric repeats inhibited DNA damage checkpoint signaling from adjacent double-strand breaks (DSBs); cell cycle arrest lasted 8-12 h from a normal DSB, whereas it lasted only 1-2 h from a DSB adjacent to a telomeric repeat. The shortened or abridged arrest was not the result of DNA repair, nor reduced amounts of single-stranded DNA, nor of adaptation. The molecular identity of this telomere repeat-associated anticheckpoint activity is unknown, though it is not dependent upon telomerase or telomere-proximal gene silencing. The anticheckpoint may inhibit the ATR yeast ortholog Mec1 because Rad9 and Rad53 became dephosphorylated and inactivated during the abridged arrest. The anticheckpoint acts regionally; it inhibited signaling from DNA breaks up to 0.6 kb away from the telomeric repeat but not from a DSB present on a separate chromosome. We propose that after formation of the DSB near the telomeric repeat, a mature telomere forms in 1-2 h, and the telomere then contains proteins that inhibit checkpoint signaling from nearby DNA breaks.

Original languageEnglish (US)
Pages (from-to)2546-2559
Number of pages14
JournalGenes and Development
Volume19
Issue number21
DOIs
StatePublished - Nov 1 2005

Fingerprint

Double-Stranded DNA Breaks
Telomere
DNA Breaks
Chromosomes
Cell Cycle Checkpoints
Single-Stranded DNA
Telomerase
Gene Silencing
DNA Repair
DNA Damage
Saccharomyces cerevisiae
Yeasts
Proteins

Keywords

  • Anticheckpoint
  • Checkpoint
  • DNA damage
  • Telomere
  • Yeast

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint. / Michelson, Rhett J.; Rosenstein, Saul; Weinert, Ted.

In: Genes and Development, Vol. 19, No. 21, 01.11.2005, p. 2546-2559.

Research output: Contribution to journalArticle

Michelson, Rhett J. ; Rosenstein, Saul ; Weinert, Ted. / A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint. In: Genes and Development. 2005 ; Vol. 19, No. 21. pp. 2546-2559.
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