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Implementation of an extrachromosomal system for the detection of novel DNA double strand break repair genes in S. cerevisiaeCaputo Galarce, Valentina January 2003 (has links)
No description available.
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Characterization of the fission yeast rad2 geneAl-Harithy, Rowyda Nawwaf January 1994 (has links)
No description available.
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The rejoining of non-homologous DNA double-strand breaks by mammalian cell free extractsMason, Rebecca Mary Aglaia January 1996 (has links)
No description available.
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DNA helicase II and exonuclease V of Escherichia coliCavanagh, David R. January 1990 (has links)
No description available.
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Molecular organisation and functional analysis of the chromosomal ruv region of Escherichia coli K12Sharples, Gary John January 1990 (has links)
No description available.
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Effects of the benzotriazine-di-N-oxide tirapazamine upon DNAWalmsley, Ray January 1995 (has links)
No description available.
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Analysis of the Escherichia coli K12 RuvC recombination proteinHagan, Nicola Frances Petrina January 1996 (has links)
No description available.
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The RusA resolvase protein of Escherichia coli K-12Chan, Sau Ngor January 1996 (has links)
No description available.
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Molecular and functional analysis of the sbcC gene of Escherichia coli K12Naom, Isam Said January 1991 (has links)
No description available.
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Hypoxia Suppresses DNA Repair: Implications for Cancer Progression and TreatmentChan, Norman 14 February 2011 (has links)
Acute and chronic hypoxia exists within the microenvironment of solid tumours and drives therapy resistance, genetic instability and metastasis. Despite its importance in solid tumour progression, very little is known regarding the functional consequences of hypoxia-mediated changes in the expression of DNA repair proteins. I studied the relationship between hypoxia and DNA repair using a prolonged chronic hypoxic gas treatment model in a variety of human tumour cell lines to mimic the dynamic state of proliferation and DNA repair in cells distant from the tumour blood vasculature.
I observed decreased expression of homologous recombination (HR) and base excision repair (BER) proteins due to a novel mechanism involving decreased protein synthesis. Error-free HR was suppressed 3-fold under 0.2% O2 as measured by the DR-GFP reporter system and functional BER was impaired as assessed with a functional glycosylase assay. This decrease in protein expression and function resulted in increased sensitivity to the DNA damaging agents MMC, cisplatin, H2O2 and MMS. Additionally, chronically hypoxic cells were relatively radiosensitive (OER = 1.37) when compared to acutely hypoxic or anoxic cells (OER = 1.96 - 2.61).
As HR defects are synthetically lethal with poly(ADP-ribose) polymerase 1 (PARP1) inhibition, I evaluated the sensitivity of repair-defective hypoxic cells to PARP inhibition. I observed increased clonogenic killing in HR-deficient hypoxic cells following inhibition or depletion of PARP1. PARP-inhibited hypoxic cells accumulated γH2AX foci consistent with an accumulation of collapsed replication forks. Additionally, tumour xenografts exposed to PARP1 inhibition showed increased γH2AX and cleaved caspase-3 expression in hypoxic subregions with suppressed RAD51 protein expression and decreased ex vivo clonogenic survival.
I conclude that persistent down-regulation of DNA repair components by the microenvironment could result in faulty DNA repair with significant implications for therapeutic response and genetic instability in human cancers. Specifically, hypoxic cells may be sensitized to PARP inhibitors and other agents targeting repair pathways down-regulated by hypoxia as a consequence of microenvironment-mediated “contextual synthetic lethality”.
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