Work

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

Year: 2005

Type: preprint

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.

Source: Genes & Development

DOI: 10.1101/gad.1293805

Authors: Rhett J. Michelson, Saul Rosenstein, Ted Weinert

Institution: University of Arizona

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

Open Access status: bronze

Funders: National Science Foundation, Damon Runyon Cancer Research Foundation

Award: Fragile Chromosome Instability and Cell Cycle Checkpoint Genes