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Mutagenesis associated with DNA seco...

Hashem, Vera Issam.

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Mutagenesis associated with DNA secondary structure: Consequences for human disease.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mutagenesis associated with DNA secondary structure: Consequences for human disease./
Author:	Hashem, Vera Issam.
Description:	237 p.
Notes:	Adviser: Richard R. Sinden.
Contained By:	Dissertation Abstracts International63-09B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3064063
ISBN:	0493827277

Mutagenesis associated with DNA secondary structure: Consequences for human disease.
Hashem, Vera Issam.

Mutagenesis associated with DNA secondary structure: Consequences for human disease. - 237 p.

Adviser: Richard R. Sinden.

Thesis (Ph.D.)--The Texas A&M University System Health Science Center, 2002.

Maintenance of DNA integrity is essential for survival of the organism. Many factors can compromise that integrity including both the DNA sequence itself and defective metabolic processes. One third of the human genome is composed of DNA repeats, including mono, di-, tri-, and tetranucleotide repeats, as well as direct and inverted repeats. Palindromic DNA is an intrinsic part of many genomes, and its ability to adopt alternative DNA structures makes it prone to genomic changes. These sequences can inherently form secondary structures that promote instability, which can lead to disease. Normally, a cell contains essential functions such as DNA repair and recombinational mechanisms that maintain DNA integrity, and thus, the functionality of the genome. Certain factors affect this integrity. Environmental and therapeutic agents can affect the stability of repeated DNA, as can mutations in certain genes involved in replication, repair and recombination. Understanding the effect that secondary structures may have on DNA integrity during DNA replication and what factors may influence their mutagenic potential are imperative for understanding disease mechanisms and for developing possible treatments. I investigated the effects of several secondary structure forming sequences on mutagenesis and explored factors that lead to an increase in mutagenesis. We found an effect of certain proteins involved in replication, DNA repair and recombination, including RecA, UvrA, UvrB, SbcC, MutS and LexA, on instability associated with trinucleotide repeat sequences. We further investigated the effect of certain genotoxicants and anti-cancer agents on the rate of deletion of trinucleotide repeat sequences. Results from these experiments suggest a therapeutic benefit of certain anticancer agents in the treatment of trinucleotide repeat expansion diseases.

ISBN: 0493827277Subjects--Topical Terms:

1017730
Biology, Genetics.

Mutagenesis associated with DNA secondary structure: Consequences for human disease.
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035 $a (UnM)AAI3064063
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100 1 $a Hashem, Vera Issam. $3 1250792
245 1 0 $a Mutagenesis associated with DNA secondary structure: Consequences for human disease.
300 $a 237 p.
500 $a Adviser: Richard R. Sinden.
500 $a Source: Dissertation Abstracts International, Volume: 63-09, Section: B, page: 4033.
502 $a Thesis (Ph.D.)--The Texas A&M University System Health Science Center, 2002.
520 $a Maintenance of DNA integrity is essential for survival of the organism. Many factors can compromise that integrity including both the DNA sequence itself and defective metabolic processes. One third of the human genome is composed of DNA repeats, including mono, di-, tri-, and tetranucleotide repeats, as well as direct and inverted repeats. Palindromic DNA is an intrinsic part of many genomes, and its ability to adopt alternative DNA structures makes it prone to genomic changes. These sequences can inherently form secondary structures that promote instability, which can lead to disease. Normally, a cell contains essential functions such as DNA repair and recombinational mechanisms that maintain DNA integrity, and thus, the functionality of the genome. Certain factors affect this integrity. Environmental and therapeutic agents can affect the stability of repeated DNA, as can mutations in certain genes involved in replication, repair and recombination. Understanding the effect that secondary structures may have on DNA integrity during DNA replication and what factors may influence their mutagenic potential are imperative for understanding disease mechanisms and for developing possible treatments. I investigated the effects of several secondary structure forming sequences on mutagenesis and explored factors that lead to an increase in mutagenesis. We found an effect of certain proteins involved in replication, DNA repair and recombination, including RecA, UvrA, UvrB, SbcC, MutS and LexA, on instability associated with trinucleotide repeat sequences. We further investigated the effect of certain genotoxicants and anti-cancer agents on the rate of deletion of trinucleotide repeat sequences. Results from these experiments suggest a therapeutic benefit of certain anticancer agents in the treatment of trinucleotide repeat expansion diseases.
590 $a School code: 1388.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Health Sciences, Pathology. $3 1017854
690 $a 0317
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710 2 0 $a The Texas A&M University System Health Science Center. $3 1250793
773 0 $t Dissertation Abstracts International $g 63-09B.
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790 1 0 $a Sinden, Richard R., $e advisor
791 $a Ph.D.
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