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Defining the role of DNA secondary s...

Dexheimer, Thomas Steven.

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Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression./
Author:	Dexheimer, Thomas Steven.
Description:	188 p.
Notes:	Adviser: Laurence H. Hurley.
Contained By:	Dissertation Abstracts International67-05B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3219737
ISBN:	9780542688928

Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression.
Dexheimer, Thomas Steven.

Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression. - 188 p.

Adviser: Laurence H. Hurley.

Thesis (Ph.D.)--The University of Arizona, 2006.

In this dissertation, we explore the transcriptional regulatory roles of G-quadruplex-forming motifs and the involvement of specific transcriptional factors, which interact with the same elements, in the control of human c-myc and bcl-2 gene expression.

ISBN: 9780542688928Subjects--Topical Terms:

1017719
Biology, Molecular.

Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression.
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020 $a 9780542688928
035 $a (UMI)AAI3219737
035 $a AAI3219737
040 $a UMI $c UMI
100 1 $a Dexheimer, Thomas Steven. $3 1287117
245 1 0 $a Defining the role of DNA secondary structures and transcriptional factors in the control of c-myc and bcl-2 expression.
300 $a 188 p.
500 $a Adviser: Laurence H. Hurley.
500 $a Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2497.
502 $a Thesis (Ph.D.)--The University of Arizona, 2006.
520 $a In this dissertation, we explore the transcriptional regulatory roles of G-quadruplex-forming motifs and the involvement of specific transcriptional factors, which interact with the same elements, in the control of human c-myc and bcl-2 gene expression.
520 $a The G-quadruplex structures within the NHE III1 region of the c-myc promoter and their ability to repress transcription has been well established. However, a longstanding unanswered question is how these stable DNA secondary structures are transformed to activate c-myc transcription. NDPK-B has been recognized as an activator of c-myc transcription via interactions with NHE III1 region of the c-myc gene promoter. Through the use of RNAi, we confirmed the transcriptional regulatory role of NDPK-B. We demonstrate that NDPK-B has DNA binding activity and the nuclease activity results from a contaminating protein. NDPK-B preferentially binds to the single-stranded guanine-rich strand of the c-myc NHE III1. Potassium ions and G-quadruplex-interactive agents, which stabilize G-quadruplex structures, had an inhibitory effect on NDPK-B DNA binding activity. Based on our studies, we have proposed a stepwise trapping-out of the NHE III1 region in a single-stranded form, thus allowing single-stranded transcription factors to bind and activate c-myc transcription. This model provides a rationale for how the stabilization of G-quadruplexes within the c-myc gene promoter region can inhibit NDPK-B from activating c-myc transcription. Similarly, the human bcl-2 gene contains a GC-rich region within its promoter region, which is critical in the regulation of bcl-2 expression. We demonstrate that the guanine-rich strand within this region can form three intramolecular G-quadruplex structures. Based on NMR studies, the central G-quadruplex forms a mixed parallel/antiparallel structure with three tetrads connected by loops of one, seven, and three bases. The G-quadruplex structures in the bcl-2 promoter extends beyond the ability to form any one of three separate G-quadruplexes to each having the capacity to form either three or six different loop isomers. This suggests that targeting these individual structures could lead to different biological outcomes. We also found that Telomestatin upregulates bcl-2 gene expression, which we propose is a result of inhibiting the binding of the WT1 repressor protein by the formation of a drug-stabilized G-quadruplex structure.
590 $a School code: 0009.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0307
690 $a 0572
710 2 0 $a The University of Arizona. $3 1017508
773 0 $t Dissertation Abstracts International $g 67-05B.
790 $a 0009
790 1 0 $a Hurley, Laurence H., $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3219737