The goal of our laboratory is to understand what roles telomeres play in chromosome stability and segregation and how this information is communicated to the cell cycle machinery. We approach these problems by studying the regulation of yeast telomere length and the proteins that are part of yeast telomeric chromatin using yeast genetics and molecular biological and biochemical approaches. These studies on telomere proteins have led us into a separate project investigating how these proteins regulate yeast life span.
Our lab developed a novel, inducible telomere formation system in the fission yeast Schizosaccharomyces pombe, and has used it do monitor the kinetics of telomere formation and the accompanying chromatin modifications (Eisenstatt, Wang et al., submitted). This novel approach produced several surprising results that will impact how chromatin domains form during differentiation or tumorigenesis, which can be investigated with our new system.
Our lab also studies lifespan regulation, and we recently discovered a cyclin dependent kinase (cdk) pathway conserved in yeast and humans (Chen, Li, Eisenstatt, Runge, 2013). We found that this cdk and its downstream effector kinase also affect autophagy, a process for digesting and recycling cellular components that is linked to lifespan extension.
A current project uses chemical genomics and mass spectrometry to identify the proteins that are specifically phosphorylated by this pathway. We will then use yeast genomic tools and high-throughput assays to identify the substrates most important to lifespan and autophagy regulation. As substrate identification is performed biochemically, we plan to use the same methodology to identify the substrates of this pathway in different mammalian tissues.
- Chen BR, Li Y, Eisenstatt JR, Runge KW. Identification of a lifespan extending mutation in the Schizosaccharomyces pombe cyclin gene clg1+ by direct selection of long-lived mutants. PLoS One. 2013 Jul 9;8(7):e69084. PMID: 23874875
- Sunder S, Greeson-Lott NT, Runge KW, Sanders SL. A new method to efficiently induce a site-specific double-strand break in the fission yeast Schizosaccharomyces pombe. Yeast. 2012 Jul;29(7):275-91. PMID: 22674789
- Hector RE, Ray A, Chen BR, Shtofman R, Berkner KL, Runge KW. Mec1p associates with functionally compromised telomeres. Chromosoma. 2012 Jun;121(3):277-90. PMID: 22289863
- Abdallah, P., Luciano, P., Runge, K.W., Lisby, M., Géli, V., Gilson, E., and Teixeira, M.T. (2009) A two-step model for senescence triggered by a single critically short telomere. Nat Cell Biol. 11, 988-993. Erratum in: Nat Cell Biol. 2010 May;12(5):520.
- Chen, B.R., and Runge, K.W. (2009) A new Schizosaccharomyces pombe chronological lifespan assay reveals that caloric restriction promotes efficient cell cycle exit and extends longevity. Exp Gerontol. 44, 493-502. PMCID: PMC2795633.
- Hector, R.E., Shtofman, R.L., Ray, A., Chen, B.R., Nyun, T., Berkner, K.L. and Runge, K.W. (2007) Tel1p preferentially associates with short telomeres to stimulate their elongation. Mol Cell. 27, 851-858.
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