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Building an episomal model of aging ...

Falcon, Alaric Antonio.

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Building an episomal model of aging in Saccharomyces cerevisiae.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Building an episomal model of aging in Saccharomyces cerevisiae./
Author:	Falcon, Alaric Antonio.
Description:	117 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2775.
Contained By:	Dissertation Abstracts International65-06B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3136937
ISBN:	0496841335

Building an episomal model of aging in Saccharomyces cerevisiae.
Falcon, Alaric Antonio.

Building an episomal model of aging in Saccharomyces cerevisiae. - 117 p.

Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2775.

Thesis (Ph.D.)--University of Florida, 2004.

Aging in Saccharomyces cerevisiae is under the control of multiple pathways. The production and accumulation of extrachromosomal rDNA circles (ERCs) is one pathway that has been proposed to bring about aging in yeast. To test this proposal, we developed a plasmid-based model system to study the role of DNA episomes in reduction of yeast life span. Recombinant plasmids containing different replication origins, cis-acting partitioning elements, and selectable marker genes were constructed and analyzed for their effects on yeast replicative life span. Plasmids containing the ARS1 replication origin reduce life span to the greatest extent of the plasmids analyzed. This reduction in life span is partially suppressed by a CEN4 centromeric element on ARS1 plasmids. Plasmids containing a replication origin from the endogenous yeast 2 micron circle also reduce life span, but to a lesser extent than ARS1 plasmids. Consistent with this, ARS1 and 2 micron origin plasmids accumulate in &sim;7-generation-old cells, but ARS1/CEN4 plasmids do not. Importantly, ARS1 plasmids accumulate to higher levels in old cells than 2 micron origin plasmids, suggesting a correlation between plasmid accumulation and life span reduction. Reduction in life span is not an indirect effect of increased ERC levels, nor the result of stochastic cessation of growth. The presence of a fully functional 9.1 kb rDNA repeat on plasmids is not required for, and does not augment, reduction in life span. These findings support the view that accumulation of DNA episomes, including ERCs, cause cell senescence in yeast.

ISBN: 0496841335Subjects--Topical Terms:

1017719
Biology, Molecular.

Building an episomal model of aging in Saccharomyces cerevisiae.
LDR:03160nmm 2200313 4500 001 1851367
005 20051216110251.5
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020 $a 0496841335
035 $a (UnM)AAI3136937
035 $a AAI3136937
040 $a UnM $c UnM
100 1 $a Falcon, Alaric Antonio. $3 1939259
245 1 0 $a Building an episomal model of aging in Saccharomyces cerevisiae.
300 $a 117 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2775.
500 $a Chair: John P. Aris.
502 $a Thesis (Ph.D.)--University of Florida, 2004.
520 $a Aging in Saccharomyces cerevisiae is under the control of multiple pathways. The production and accumulation of extrachromosomal rDNA circles (ERCs) is one pathway that has been proposed to bring about aging in yeast. To test this proposal, we developed a plasmid-based model system to study the role of DNA episomes in reduction of yeast life span. Recombinant plasmids containing different replication origins, cis-acting partitioning elements, and selectable marker genes were constructed and analyzed for their effects on yeast replicative life span. Plasmids containing the ARS1 replication origin reduce life span to the greatest extent of the plasmids analyzed. This reduction in life span is partially suppressed by a CEN4 centromeric element on ARS1 plasmids. Plasmids containing a replication origin from the endogenous yeast 2 micron circle also reduce life span, but to a lesser extent than ARS1 plasmids. Consistent with this, ARS1 and 2 micron origin plasmids accumulate in &sim;7-generation-old cells, but ARS1/CEN4 plasmids do not. Importantly, ARS1 plasmids accumulate to higher levels in old cells than 2 micron origin plasmids, suggesting a correlation between plasmid accumulation and life span reduction. Reduction in life span is not an indirect effect of increased ERC levels, nor the result of stochastic cessation of growth. The presence of a fully functional 9.1 kb rDNA repeat on plasmids is not required for, and does not augment, reduction in life span. These findings support the view that accumulation of DNA episomes, including ERCs, cause cell senescence in yeast.
520 $a The endogenous 2 micron circle is a naturally occurring episomal DNA. Loss of the 2 micron circle can be facilitated with the transformation of an ARS containing plasmid. Since 2 micron circles are episomes, and episomes can cause aging, experiments were complete to show that it does not accumulate in old cells and does not cause aging.
520 $a In strains that contain more ERCs, ARS plasmids do not accumulate as much. There is an episomal competition phenomenon. While it is not known what the episomes are competing for, it can be demonstrated that as the number of different episomes increase the rate of accumulation for each episome decreases.
590 $a School code: 0070.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
690 $a 0307
690 $a 0379
690 $a 0369
710 2 0 $a University of Florida. $3 718949
773 0 $t Dissertation Abstracts International $g 65-06B.
790 1 0 $a Aris, John P., $e advisor
790 $a 0070
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3136937