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Molecular and Cellular Biology, January 2004, p. 837-845, Vol. 24, No. 2
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.2.837-845.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Telomere Cap Components Influence the Rate of Senescence in Telomerase-Deficient Yeast Cells

Shinichiro Enomoto, Lynn Glowczewski, Jodi Lew-Smith, and Judith G. Berman^*

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455

Received 4 August 2003/ Returned for modification 3 September 2003/ Accepted 8 October 2003

Cells lacking telomerase undergo senescence, a progressive reduction in cell division that involves a cell cycle delay and culminates in "crisis," a period when most cells become inviable. In telomerase-deficient Saccharomyces cerevisiae cells lacking components of the nonsense-mediated mRNA decay (NMD) pathway (Upf1,Upf2, or Upf3 proteins), senescence is delayed, with crisis occurring 10 to 25 population doublings later than in Upf⁺ cells. Delayed senescence is seen in upf cells lacking the telomerase holoenzyme components Est2p and TLC1 RNA, as well as in cells lacking the telomerase regulators Est1p and Est3p. The delay of senescence in upf cells is not due to an increased rate of survivor formation. Rather, it is caused by alterations in the telomere cap, composed of Cdc13p, Stn1p, and Ten1p. In upf mutants, STN1 and TEN1 levels are increased. Increasing the levels of Stn1p and Ten1p in Upf⁺ cells is sufficient to delay senescence. In addition, cdc13-2 mutants exhibit delayed senescence rates similar to those of upf cells. Thus, changes in the telomere cap structure are sufficient to affect the rate of senescence in the absence of telomerase. Furthermore, the NMD pathway affects the rate of senescence in telomerase-deficient cells by altering the stoichiometry of telomere cap components.

Present address: Department of Veterinary Pathobiology, University of Minnesota, St Paul, MN 55108.

Present address: Proteome Division, Incyte Genomics, Inc., Beverly, MA 01915.

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