EXO1 Plays a Role in Generating Type I and Type II Survivors in Budding Yeast

Corresponding author: David Lydall, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom., d.a.lydall{at}ncl.ac.uk (E-mail)

Communicating editor: A. NICOLAS

Telomerase-defective budding yeast cells escape senescence by using homologous recombination to amplify telomeric or subtelomeric structures. Similarly, human cells that enter senescence can use homologous recombination for telomere maintenance, when telomerase cannot be activated. Although recombination proteins required to generate telomerase-independent survivors have been intensively studied, little is known about the nucleases that generate the substrates for recombination. Here we demonstrate that the Exo1 exonuclease is an initiator of the recombination process that allows cells to escape senescence and become immortal in the absence of telomerase. We show that EXO1 is important for generating type I survivors in yku70 mre11 cells and type II survivors in tlc1 cells. Moreover, in tlc1 cells, EXO1 seems to contribute to the senescence process itself.

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