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Silent chromatin dynamics upon major metabolic transitions

Abstract : The tri-dimensional organization of the genome emerges as an important, still poorly understood, control mechanism in genomic function. Studies in S. cerevisiae have broadly contributed to demonstrate the functional importance of nuclear organization. Upon logaritmic growth, the 16 chromosomes of a S. cerevisiae haploid nucleus are organized into the Rabl conformation, with centromeres bound at the SPB and telomeres grouped in 3-4 foci localized at the nuclear periphery. Telomere clusters allow the concentration of silencing proteins (SIRs) and appear important for genome functions. The aim of my doctorate work was to study telomeric silent chromatin upon major metabolic transitions. We found that the genome of long-lived quiescent cells undergoes a major spatial re-organization following carbon source exhaustion. This change in nuclear architecture is driven by the grouping of telomeres into a unique focus (hypercluster) localized in the center of the nucleus. We also show that this reorganization is a programmed event triggered by reactive oxigen species (ROS) produced upon early respiration and involves the DNA damage checkpoint pathway. Finally, we report that excess of Sir2 activity counteracts telomere clustering upon quiescence and has a negative role on chronological life span. Our work suggests that the drastic genome reorganization due to telomere grouping favors survival upon quiescence, and unravels a novel connection between metabolism, nuclear organization and aging.
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Submitted on : Wednesday, December 20, 2017 - 9:38:27 AM
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  • HAL Id : tel-01668453, version 1


Micol Guidi. Silent chromatin dynamics upon major metabolic transitions. Cellular Biology. Université Pierre et Marie Curie - Paris VI, 2015. English. ⟨NNT : 2015PA066609⟩. ⟨tel-01668453⟩



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