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![The Effect of Skewed Elevation in dNTP Pools on Loss of Heterozygosity in Saccharomyces cerevisiae için kapak resmi The Effect of Skewed Elevation in dNTP Pools on Loss of Heterozygosity in Saccharomyces cerevisiae için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
The Effect of Skewed Elevation in dNTP Pools on Loss of Heterozygosity in Saccharomyces cerevisiae
Başlık:
The Effect of Skewed Elevation in dNTP Pools on Loss of Heterozygosity in Saccharomyces cerevisiae
Yazar:
Badar, Jumana, author.
ISBN:
9780438048805
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (97 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Jennifer A. Surtees Committee members: Michael Buck; Mark D. Sutton.
Özet:
DNA precursors, deoxyribonucleotide triphosphates (dNTP), are the basic components of DNA. Enzyme ribonucleotide reductase (RNR) tightly regulates the levels of dNTP pools to ensure high fidelity DNA replication and repair. Misregulated levels of dNTP pools cause mutagenesis which impacts genome stability and cellular fitness; characteristics of cancer cells. Even though, a basic causal relationship between elevated dNTP pools and genomic instability has been established, some of the underlying mechanisms remain poorly understood.
This project highlights replication fork stability as a determinant of genomic integrity in the presence of skewed and elevated dNTP pools. Double strand breaks associated with unstable replication forks are primarily repaired via homologous recombination (HR) in Saccharomyces cerevisiae. HR can cause loss of chromosomal regions; termed loss of heterozygosity (LOH) in heterozygous chromosomes. This study shows that skewed and elevated dNTP pools cause a reduction in LOH events. Lowered LOH is not a result of decreased survivability; results show the latter is not affected in the presence of elevated dNTP pools.
The results are consistent with a previous study wherein low levels of dNTP pools were shown to slow replication fork and increase fork stalling. Alternatively, with elevated dNTP pools, DNA polymerases prefer DNA synthesis over proofreading. This leads to faster replication fork progression. Elevated dNTP pools also promote replication past a damaged DNA template; continuing faster DNA synthesis. This study proposes a model where a skewed elevation in dNTP pools either reduces the number of replication fork stalls/collapses by faster fork progression or uses an alternative non-homologous repair pathway to fix an unstable fork.
Notlar:
School code: 0656
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(693942.1) | 693942-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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