Metabolic regulation of telomere structure and cellular senescence
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About the talk: Cellular senescence is a permanent form of cell cycle arrest triggered by accumulated stochastic damage to cells. Dysregulation of cellular metabolism and epigenetic modifications are two important hallmarkers of cellular senescence. We have previously identified pyruvate kinase (Pyk1) as a moonlighting protein that coordinates cell metabolism and histone modifications by forming a complex named SESAME. Here, we identified two novel functions of SESAME in regulating telomere structure and ageing. SESAME phosphorylates H3T11 at telomeres, which prevents SIR complex from being degradation by autophagy and promotes SIR complex assembly at telomeres. SESAME also interacts with the histone acetyltransferase SAS complex to promote histone H4K16ac enrichment at subtelomere regions and maintain telomere silencing. Moreover, this interaction is enhanced by acetate to increase H4K16ac at subtelomere regions, leading to compromised telomere silencing and accelerated chronological ageing. Altogether, our results reveal a conserved mechanism to connect cell metabolism with telomere silencing and cellular senescence.
Speaker
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Professor Shanshan Li
Hubei University
About the speaker: Shanshan Li currently works as the professor in Hubei University. He also serves as the vice director for the State Key Laboratory of Biocatalysis and Enzyme Engineering. He obtained his Ph.D. at Iowa State University and did post-doc training at Stowers Institute for Medical Research. His research interest is understanding how glucose metabolism regulates cellular senescence and tumorigenesis ..About the speaker: Shanshan Li currently works as the professor in Hubei University. He also serves as the vice director for the State Key Laboratory of Biocatalysis and Enzyme Engineering. He obtained his Ph.D. at Iowa State University and did post-doc training at Stowers Institute for Medical Research. His research interest is understanding how glucose metabolism regulates cellular senescence and tumorigenesis. He is particularly interested in identifying the non-metabolic functions of metabolic enzymes in regulating epigenetic modifications. Using budding yeast, C. elegans and mice as model organisms, he also aims to identify small molecules that can act as signal molecules to delay ageing and inhibit tumorigenesis.
