): Oxidative DNA damage induced by reactive oxygen species has been associated with aging and age-elated diseases, as well as several forms of human cancer. 8-Oxoguanine is a lesion that has been used as a marker for oxidative DNA damage. 8-Oxoguanine has been shown to be mutagenic in vivo and in vitro. Recently, mogg1, a murine 8- oxoguanine-DNA repair enzyme was cloned and over expressed in transgenic animals. Although extensive information has been accumulated on the substrate specificity and the repair mechanism of mogg1 and its isoforms, there is little information regarding their biochemical properties, regulation during the cell cycle and subcellular distribution in cells growing under normal and oxidative stress conditions. Similarly, there is little information regarding the intranuclear distribution of ogg1 and its molecular relationships with chromatin and structural components of the nucleus. We propose to address these questions by raising monospecific antibodies directed against purified b a c terially-expressed wild-type recombinant mogg1. We will use these a n t i b odies to determine the subcellular localization of mogg1 and biochemically characterize nuclear and cytoplasmic pools of the enzyme derived from mammalian tissue culture cells as well as the liver of wild-type and transgenic mice over expressing ogg1. We will also characterize the induction of oxidative DNA damage in nutrient deprived cells by determining whether levels of 8-oxoguanine correlate with the synthesis of ogg1 and heat shock proteins and evaluating the cell cycle-dependent regulation of ogg1. Finally, we will colocalize 3-oxoguanine nuclear """"""""hot spots"""""""" with ogg1, chromatin and structural protein components of the nucleus in tissue culture cells and tissues from wild-type and transgenic mice over expressing mogg1.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Scientist Development Award - Research & Training (K01)
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Subcommittee G - Education (NCI)
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Ojeifo, John O
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Conlon, Kimberly A; Berrios, Miguel (2007) Site-directed photoproteolysis of 8-oxoguanine DNA glycosylase 1 (OGG1) by specific porphyrin-protein probe conjugates: a strategy to improve the effectiveness of photodynamic therapy for cancer. J Photochem Photobiol B 87:9-17
Kemeleva, Eugenia A; Sinitsyna, Olga I; Kolosova, Nataliya G et al. (2006) Immunofluorescent detection of 8-oxoguanine DNA lesions in liver cells from aging OXYS rats, a strain prone to overproduction of free radicals. Mutat Res 599:88-97
Kemeleva, E A; Sinitsyna, O I; Conlon, K A et al. (2006) Oxidation of guanine in liver and lung DNA of prematurely aging OXYS rats. Biochemistry (Mosc) 71:612-8
Conlon, Kimberly A; Miller, Holly; Rosenquist, Thomas A et al. (2005) The murine DNA glycosylase NEIL2 (mNEIL2) and human DNA polymerase beta bind microtubules in situ and in vitro. DNA Repair (Amst) 4:419-31
Conlon, Kimberly A; Zharkov, Dmitry O; Berrios, Miguel (2004) Cell cycle regulation of the murine 8-oxoguanine DNA glycosylase (mOGG1): mOGG1 associates with microtubules during interphase and mitosis. DNA Repair (Amst) 3:1601-15
Conlon, Kimberly A; Zharkov, Dmitry O; Berrios, Miguel (2003) Immunofluorescent localization of the murine 8-oxoguanine DNA glycosylase (mOGG1) in cells growing under normal and nutrient deprivation conditions. DNA Repair (Amst) 2:1337-52
Conlon, Kimberly A; Rosenquist, Thomas; Berrios, Miguel (2002) Site-directed photochemical disruption of the actin cytoskeleton by actin-binding Rose Bengal-conjugates. J Photochem Photobiol B 68:140-6
Conlon, K A; Berrios, M (2001) Light-induced proteolysis of myosin heavy chain by Rose Bengal-conjugated antibody complexes. J Photochem Photobiol B 65:22-8