# TELOMERE REPLICATION AND SENESCENCE IN YEAST

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1993 · $177,813

## Abstract

Telomeres are specialized elements found at the termini of linear
chromosomes. They are required to protect chromosome ends from degradation
and fusion with other ends; in addition, telomeres also promote accurate
chromosome segregation. In humans, missegregation of chromosomes can lead
to a number of disorders, such as cancer and birth defects. Defects in
telomere replication in yeast and Tetrahymena lead to senescence,
suggesting that this could be a contributing factor in mammalian cellular
senescence as well.

A primary determinant for maintaining a constant chromosomal telomere
length is telomerase, identified biochemically in ciliates and humans.
Telomerase has been shown to be a novel reverse transcriptase-like enzyme
which carries an internal RNA responsible for templating the newly
synthesized telomeric DNA. Telomerase activity has not yet been
biochemically identified from a genetically tractable organism such as
yeast, which has limited the analysis of factors that interact with this
enzyme. In addition, nothing is yet known about the protein composition of
telomerase.

The long term objective of the proposed research is to dissect the
apparatus responsible for replicating telomeres, using the yeast S.
cerevisiae as a model system. A starting point for these studies is the
EST1 gene of yeast. Yeast cells lacking a functional EST1 gene show a
continuous decline in telomere length and a senescence phenotype. Although
a number of mutants of yeast have been identified which alter telomere
length, this is the only mutant of yeast which coordinately affects both
telomere length and senescence.

No exhaustive search has previously been done in any organism for genes
which, when mutated, coordinately affect telomere replication and
senescence. S. cerevisiae lends itself to such a search, both because it
is a genetically tractable system and because isolation of the est1
mutation provides a precedent for this particular class of mutations. The
first section of this proposal describes a genetic approach to identify
all other genes besides EST1 which, when mutated, coordinately affect
telomere replication and senescence; this should include the predicted
yeast telomerase RNA Recovery of such genes is an important step towards
understanding how different components involved in telomere replication
contribute to cellular senescence in a lower eukaryote. The second aim of
this research is to identify additional genes that encode components that
interact with the EST1 gene product, using three different genetic
approaches; characterization of these genes should provide additional
information about Est1 function. A third goal is to biochemically
characterize activities associated with the Est1 protein. Two hypotheses
will guide these biochemical experiments: first, that Est1 is a component
of telomerase, and second, that Est1 is a telomere binding protein.

## Key facts

- **NIH application ID:** 3123583
- **Project number:** 1R01AG011728-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** Victoria Lundblad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $177,813
- **Award type:** 1
- **Project period:** 1993-09-20 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123583

## Citation

> US National Institutes of Health, RePORTER application 3123583, TELOMERE REPLICATION AND SENESCENCE IN YEAST (1R01AG011728-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123583. Licensed CC0.

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