Journal
CELLS
Volume 10, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/cells10040778
Keywords
cell senescence; senescence regulation; sub-telomeres; telomere binding protein; Sir4; Rif1; yeast
Categories
Funding
- National Natural Science Foundation of China [31501110, 81530039]
- National Key Research and Development Program of China [2018YFC2000100]
- Start-up Research Program of Hangzhou Normal University [2018QDL010]
- China Postdoctoral Science Foundation [2014M551470]
- Postdoctoral Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2014KIP305]
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Telomere shortening leads to cellular senescence, and this study reveals a dual opposing control mechanism of sub-telomeric Y' element recombination by Sir3/4 and Rif1, regulating telomere length and cell senescence in yeast Saccharomyces cerevisiae. Sir4 repression of Y' element recombination is negatively regulated by Rif1, mediating senescence-evasion induced by Sir4 deficiency.
Telomere shortening results in cellular senescence and the regulatory mechanisms remain unclear. Here, we report that the sub-telomere regions facilitate telomere lengthening by homologous recombination, thereby attenuating senescence in yeast Saccharomyces cerevisiae. The telomere protein complex Sir3/4 represses, whereas Rif1 promotes, the sub-telomere Y ' element recombination. Genetic disruption of SIR4 increases Y ' element abundance and rescues telomere-shortening-induced senescence in a Rad51-dependent manner, indicating a sub-telomere regulatory switch in regulating organismal senescence by DNA recombination. Inhibition of the sub-telomere recombination requires Sir4 binding to perinuclear protein Mps3 for telomere perinuclear localization and transcriptional repression of the telomeric repeat-containing RNA TERRA. Furthermore, Sir4 repression of Y ' element recombination is negatively regulated by Rif1 that mediates senescence-evasion induced by Sir4 deficiency. Thus, our results demonstrate a dual opposing control mechanism of sub-telomeric Y ' element recombination by Sir3/4 and Rif1 in the regulation of telomere shortening and cell senescence.
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