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dc.contributor.author
Şengör, Hakkı Celalettin Asım
dc.contributor.supervisor
Barral, Yves
dc.contributor.supervisor
Aebi, Markus
dc.contributor.supervisor
Peter, Mathias
dc.date.accessioned
2019-11-04T11:57:17Z
dc.date.available
2019-11-04T10:28:01Z
dc.date.available
2019-11-04T11:57:17Z
dc.date.issued
2019
dc.identifier.uri
http://hdl.handle.net/20.500.11850/375126
dc.identifier.doi
10.3929/ethz-b-000375126
dc.description.abstract
Aging is a universal phenomenon that is even observed in inorganic material. In the inorganic world it is associated with damage induced weariness, yet in the organic world it presents a much more complicated and interesting case. In biology, aging is defined as the time-dependent decline in vital functions of an organism. This was inherently associated with damage accumulation over time. However, mounting evidence from recent years have provided data that are a suggestive of an alternative view. They have shown that aging might be coupled with differentiation and non-mendelian trait acquisitions (memory). Therefore, the nature of an aging factor has become more interesting over the years. Using the unicellular eukaryote Saccharomyces cerevisiae I have asked myself a simple question: What causes aging? Two types of molecules have been associated with aging in the last years: extra-chromosomal rDNA circles (ERCs) and protein aggregates. Nevertheless, it is still unknown if the behavior of one affects the other, or if one’s effect can be exclusively influential of the other. I asked if age-dependent protein aggregation and ERCs worked together or seperately. By using mutants that decrease age-dependent protein aggregation (APOD), I have observed that ERC retention is significantly altered. My results indicate that when cells fail to collect protein aggregates into one location with the help of HSP40 family chaperone Hsp42, a pathway including mitochondrial signaling is activated and the formation of the nuclear diffusion barrier is suppressed. Consequently fewer DNA-circle-attached NPCs are retained in the mother nucleus. This leads to the sharing of aging factors such as ERCs with the progeny. Additionally, a similar effect on DNA-circle segregation can be induced by changing the external nitrogen-source of the cells. My results suggest that APOD formation serves a protective role for the progeny. Furthermore, these data indicate that mitochondria are involved in sensing cytoplasmic stress and nuclear compartmentalization during mitosis. I conclude by proposing that the aging phenotypes seen in mutants with decreased protein aggregation is actually caused by effects that include ERCs. I also show that protein aggregation is part of heat-induced ethanol tolerance, and regulated by protein chaperons. Together with these results I end with a proposal that cellular aging actually is not irreversible damage accumulation, but rather an adaptation fatigue experienced by cells.

en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.subject
ageing, yeast, memory, protein aggregates, DNA-circles, ERCs, stress, saccharomyces cerevisiae
en_US
dc.title
The Relationship Between ERCs and Protein Aggregates In the Context of Replicative Aging in Saccharomyces cerevisiae
en_US
dc.type
Doctoral Thesis
dc.date.published
2019-11-04
ethz.size
121 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
ethz.identifier.diss
25859
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03532 - Barral, Yves / Barral, Yves
en_US
ethz.date.deposited
2019-11-04T10:28:16Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Embargoed
en_US
ethz.date.embargoend
2021-11-04
ethz.rosetta.installDate
2019-11-04T11:58:13Z
ethz.rosetta.lastUpdated
2021-02-15T06:33:14Z
ethz.rosetta.versionExported
true
ethz.COinS
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