Poster abstracts
Poster number 102 submitted by Taizina Momtareen
Investigating the transcriptomic changes in response to telomerase loss in Saccharomyces cerevisiae
Taizina Momtareen (West Virginia University), Jennifer Gallagher (West Virginia University)
Abstract:
Telomeres protect the genetic material at chromosome ends but progressively shorten with each cell division. In healthy cells, critically short telomeres trigger senescence and cell death, but cancerous cells use telomerase to elongate their telomeres and restart the cell cycle. ALT (Alternative Lengthening of Telomeres) cancer cells employ a recombination-based mechanism to extend their telomeres without telomerase. Similarly, some telomerase mutants of S. cerevisiae can bypass senescence through DNA recombination-based telomere elongation, forming post-senescence survivors. These survivor cells experience unregulated telomere lengthening, which leads to significant replication stress and upregulation of energy production genes (Nautiyal et al., 2002). While previous studies have examined growth rates and telomere lengths in these mutants, a detailed understanding of the factors contributing to replication stress and the cellular adaptations to overcome it remains incomplete. The aim of this study was to characterize the transcriptomic changes in tlc1- mutant yeast strains across multiple passages (P4, P7, and P10). We used RNA-seq to explore how tlc1- mutant yeast cells adapt to telomerase loss and replication stress over several generations. We identified key biological pathways such as mitochondrial function, ribosome biogenesis, stress response, and found that the regulation of these pathways varied depending on the passage. Several subtelomeric genes were also significantly differentially expressed across the passages, indicating the role of telomerase in maintaining subtelomeric stability. This study provides new insights into the molecular mechanisms of telomerase loss, with potential implications for understanding ALT and other age-related diseases in higher organisms.
References:
Nautiyal, S., DeRisi, J. L., & Blackburn, E. H. (2002). The genome-wide expression response to telomerase deletion in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences, 99(14), 9316–9321. https://doi.org/10.1073/pnas.142162499
Keywords: transcriptome, telomere