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DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p.

Abstract:
In eukaryotic cells, surveillance mechanisms detect and respond to DNA damage by triggering cell-cycle arrest and inducing the expression of DNA-repair genes [1]. In budding yeast, a single DNA double-strand break (DSB) is sufficient to trigger cell-cycle arrest [2]. One highly conserved pathway for repairing DNA DSBs is DNA non-homologous end-joining (NHEJ), which depends on the DNA end-binding protein Ku [3]. NHEJ also requires the SIR2, SIR3 and SIR4 gene products [4] [5], which are responsible for silencing at telomeres and the mating-type loci [6]. Because of the link between NHEJ and the Sir proteins, we investigated whether DNA damage influences telomeric silencing. We found that DNA damage triggers the reversible loss of telomeric silencing and relocation of Sir3p from telomeres. Complete Sir3p relocation was triggered by a single DNA DSB, suggesting that the singal is amplified. Consistent with this idea, Sir3p relocation depended on the DNA damage-signalling components Ddc1p and Mec1p. Thus, signalling of DNA damage may release Sir3p from telomeres and permit its subsequent association with other nuclear subdomains to regulate transcription, participate in DNA repair and/or enhance genomic stability by other mechanisms.
Authors:
AD McAinsh, S Scott-Drew, JA Murray, SP Jackson
Journal:
Curr Biol
Citation info:
9(17):963-966
Publication date:
9th Sep 1999
Full text
DOI