國立高雄大學圖資館 |

登入

回首頁

Dissecting the Regulators of DNA Replication Timing.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Dissecting the Regulators of DNA Replication Timing.
作者:	Vouzas, Athanasios.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, 2023
面頁冊數:	107 p.
附註:	Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
附註:	Advisor: Bass, Henry W.
Contained By:	Dissertations Abstracts International85-03B.
標題:	Biology.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30527611
ISBN:	9798380415484

Dissecting the Regulators of DNA Replication Timing.
Vouzas, Athanasios.

Dissecting the Regulators of DNA Replication Timing. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 107 p.

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

Thesis (Ph.D.)--The Florida State University, 2023.

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

During S-phase, the mammalian genome replicates in a defined temporal order called the DNA Replication Timing (RT) program. This program is developmentally regulated and is perturbed in diseased cell states, such as cancers and progeria. In recent years, the field has uncovered multiple layers of regulation of the RT program. These layers of regulation range from genome wide (Rif1), to chromosome wide (ASARs) and domain wide (ERCEs). Transcription is a process in the nucleus that tightly correlates with RT and has been suggested to be yet another way the cell regulates its RT program. Here I used a systematic approach to investigate how ectopic insertions of a series of transcription units in a late replicating domain influences the RT of that domain. Through this work, I show that transcription of a small gene is not sufficient to induce a RT advance. Since the only difference between the transcription units used in this study is the promoter itself, I posit that the local epigenetic environment built around the inserted promoter is critical for the ability of the promoter to induce a RT advance. Additionally, I present evidence that transcriptional activation using an inducible promoter can lead to a controlled RT advance. We also identified and characterized chromosome wide regulators of DNA RT, Asynchronous Replication and Autosomal RNAs (ASARs), across human autosomes. Utilizing the known features of ASARs, we identified 68 transcribed loci across human autosomes as candidate ARARs with allelic expression imbalance and asynchronous RT. Indeed, we discovered that five of these 68 transcribed loci share the characteristics and functionality of ASARs and classified them as novel ASARs. We further decoupled the RT of any particular ASAR allele from the RTs of the other allele, other ASARs on the same chromosome, and RT genome wide. Importantly, we showed that the RT of an ASAR allele was independent of the expression profile of the allele, which indicates that transcription is neither necessary nor sufficient to induce early DNA replication of the ASAR.

ISBN: 9798380415484Subjects--Topical Terms:

188667
Biology.
Subjects--Index Terms:

Asynchronous Replication and Autosomal RNAs

Dissecting the Regulators of DNA Replication Timing.
LDR:03283nmm a2200385 4500 001 655798
005 20240414211933.5
006 m o d
007 cr#unu||||||||
008 240620s2023 ||||||||||||||||| ||eng d
020 $a 9798380415484
035 $a (MiAaPQ)AAI30527611
035 $a AAI30527611
040 $a MiAaPQ $c MiAaPQ
100 1 $a Vouzas, Athanasios. $0 (orcid)0009-0007-1482-9919 $3 966887
245 1 0 $a Dissecting the Regulators of DNA Replication Timing.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 107 p.
500 $a Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
500 $a Advisor: Bass, Henry W.
502 $a Thesis (Ph.D.)--The Florida State University, 2023.
506 $a This item must not be sold to any third party vendors.
520 $a During S-phase, the mammalian genome replicates in a defined temporal order called the DNA Replication Timing (RT) program. This program is developmentally regulated and is perturbed in diseased cell states, such as cancers and progeria. In recent years, the field has uncovered multiple layers of regulation of the RT program. These layers of regulation range from genome wide (Rif1), to chromosome wide (ASARs) and domain wide (ERCEs). Transcription is a process in the nucleus that tightly correlates with RT and has been suggested to be yet another way the cell regulates its RT program. Here I used a systematic approach to investigate how ectopic insertions of a series of transcription units in a late replicating domain influences the RT of that domain. Through this work, I show that transcription of a small gene is not sufficient to induce a RT advance. Since the only difference between the transcription units used in this study is the promoter itself, I posit that the local epigenetic environment built around the inserted promoter is critical for the ability of the promoter to induce a RT advance. Additionally, I present evidence that transcriptional activation using an inducible promoter can lead to a controlled RT advance. We also identified and characterized chromosome wide regulators of DNA RT, Asynchronous Replication and Autosomal RNAs (ASARs), across human autosomes. Utilizing the known features of ASARs, we identified 68 transcribed loci across human autosomes as candidate ARARs with allelic expression imbalance and asynchronous RT. Indeed, we discovered that five of these 68 transcribed loci share the characteristics and functionality of ASARs and classified them as novel ASARs. We further decoupled the RT of any particular ASAR allele from the RTs of the other allele, other ASARs on the same chromosome, and RT genome wide. Importantly, we showed that the RT of an ASAR allele was independent of the expression profile of the allele, which indicates that transcription is neither necessary nor sufficient to induce early DNA replication of the ASAR.
590 $a School code: 0071.
650 4 $a Biology. $3 188667
650 4 $a Genetics. $3 189015
650 4 $a Molecular biology. $3 188737
653 $a Asynchronous Replication and Autosomal RNAs
653 $a DNA Replication Timing
653 $a Transcription
653 $a Genome wide
690 $a 0306
690 $a 0369
690 $a 0307
710 2 $a The Florida State University. $b Biological Science. $3 966888
773 0 $t Dissertations Abstracts International $g 85-03B.
790 $a 0071
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30527611