國立虎尾科技大學 |

Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae./
Author:	Salim, Devika.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	315 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-11, Section: B.
Contained By:	Dissertations Abstracts International81-11B.
Subject:	Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27969070
ISBN:	9798607313616

Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae.
Salim, Devika.

Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 315 p.

Source: Dissertations Abstracts International, Volume: 81-11, Section: B.

Thesis (Ph.D.)--Open University (United Kingdom), 2020.

This item must not be sold to any third party vendors.

Tandem repeats are inherently unstable and exhibit extensive copy number polymorphisms. Despite mounting evidence for their adaptive potential, the mechanisms associated with regulation of the stability and copy number of tandem repeats remain largely unclear. To study copy number variation at tandem repeats, I used two well-studied repetitive arrays in the budding yeast genome, the ribosomal DNA (rDNA) locus, and the copper-inducible CUP1 gene array. I developed powerful, highly sensitive assays to measure repeat instability and copy number and used them in multiple high-throughput genetic screens to define pathways involved in regulating rDNA copy number variation. These screens revealed that rDNA stability and copy number are regulated by DNA replication, transcription, and histone acetylation. Through parallel studies of the CUP1 array, I showed that instability at both tandem arrays can be induced by DNA replication stress and altered transcription of the locus. Importantly, while changes in instability in response to stress are observed within a few cell divisions, a change in steady state repeat copy number requires selection. Further, H3K56 acetylation is required for regulating transcription and transcription-induced instability at the CUP1 array, and, importantly, it restricts transcription-induced amplification of the CUP1 array. My work suggests that the modulation of replication and transcription is a simple, reversible strategy to alter instability at tandem repeats in response to environmental stimuli, which provides cells rapid adaptability through copy number variation. Additionally, histone acetylation may function to promote the normal adaptive program in response to transcriptional stress. Given the ubiquity of DNA replication, transcription, and chromatin marks like histone acetylation, the mechanisms I have characterized could significantly advance our understanding of the behavior of other tandem repeats and their role in shaping eukaryotic genomes.

ISBN: 9798607313616Subjects--Topical Terms:

591510
Microbiology.
Subjects--Index Terms:

Stability

Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae.
LDR:03152nam a2200349 4500 001 1037977
005 20210910100646.5
008 211029s2020 ||||||||||||||||| ||eng d
020 $a 9798607313616
035 $a (MiAaPQ)AAI27969070
035 $a (MiAaPQ)Open_Univ_UK69961
035 $a AAI27969070
040 $a MiAaPQ $c MiAaPQ
100 1 $a Salim, Devika. $3 1335295
245 1 0 $a Regulation of Stability and Copy Number of Tandem Repeats in Saccharomyces cerevisiae.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 315 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-11, Section: B.
500 $a Advisor: Gerton, Jennifer .
502 $a Thesis (Ph.D.)--Open University (United Kingdom), 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Tandem repeats are inherently unstable and exhibit extensive copy number polymorphisms. Despite mounting evidence for their adaptive potential, the mechanisms associated with regulation of the stability and copy number of tandem repeats remain largely unclear. To study copy number variation at tandem repeats, I used two well-studied repetitive arrays in the budding yeast genome, the ribosomal DNA (rDNA) locus, and the copper-inducible CUP1 gene array. I developed powerful, highly sensitive assays to measure repeat instability and copy number and used them in multiple high-throughput genetic screens to define pathways involved in regulating rDNA copy number variation. These screens revealed that rDNA stability and copy number are regulated by DNA replication, transcription, and histone acetylation. Through parallel studies of the CUP1 array, I showed that instability at both tandem arrays can be induced by DNA replication stress and altered transcription of the locus. Importantly, while changes in instability in response to stress are observed within a few cell divisions, a change in steady state repeat copy number requires selection. Further, H3K56 acetylation is required for regulating transcription and transcription-induced instability at the CUP1 array, and, importantly, it restricts transcription-induced amplification of the CUP1 array. My work suggests that the modulation of replication and transcription is a simple, reversible strategy to alter instability at tandem repeats in response to environmental stimuli, which provides cells rapid adaptability through copy number variation. Additionally, histone acetylation may function to promote the normal adaptive program in response to transcriptional stress. Given the ubiquity of DNA replication, transcription, and chromatin marks like histone acetylation, the mechanisms I have characterized could significantly advance our understanding of the behavior of other tandem repeats and their role in shaping eukaryotic genomes.
590 $a School code: 0949.
650 4 $a Microbiology. $3 591510
653 $a Stability
653 $a Copy number
653 $a Tandem repeats
653 $a Saccharomyces cerevisiae
690 $a 0410
710 2 $a Open University (United Kingdom). $3 1335296
773 0 $t Dissertations Abstracts International $g 81-11B.
790 $a 0949
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27969070