CELL BIOLOGY OF OXIDATIVE DNA DAMAGE AND REPAIR

DNA 氧化损伤和修复的细胞生物学

• 批准号: 6739039
• 负责人: MIGUEL BERRIOS
• 金额: $ 15.97万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739039
• 关键词: DNA damage; DNA repair; HeLa cells; cell cycle; chromatin; complementary DNA; endonuclease; enzyme activity; enzyme induction /repression; free radical oxygen; genetically modified animals; guanine analog; heat shock proteins; laboratory mouse; laboratory rabbit; oxidative stress; recombinant proteins

DESCRIPTION (Applicant's Description): 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.

描述（申请人描述）：氧化性DNA损伤由

项目成果

Site-directed photochemical disruption of the actin cytoskeleton by actin-binding Rose Bengal-conjugates.

通过与肌动蛋白结合的玫瑰红缀合物对肌动蛋白细胞骨架进行定点光化学破坏。

• DOI: 10.1016/s1011-1344(02)00382-2
• 发表时间: 2002
• 期刊: Journal of photochemistry and photobiology. B, Biology
• 作者: Conlon,KimberlyA;Rosenquist,Thomas;Berrios,Miguel
• 通讯作者: Berrios,Miguel

Light-induced proteolysis of myosin heavy chain by Rose Bengal-conjugated antibody complexes.

• DOI: 10.1016/s1011-1344(01)00241-x
• 发表时间: 2001-12
• 期刊: Journal of photochemistry and photobiology. B, Biology
• 作者: K. Conlon;M. Berrios

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.

通过特定的卟啉-蛋白质探针结合物对 8-氧代鸟嘌呤 DNA 糖基化酶 1 (OGG1) 进行定点光蛋白水解：提高癌症光动力疗法有效性的策略。

• DOI: 10.1016/j.jphotobiol.2006.12.004
• 发表时间: 2007
• 期刊: Journal of photochemistry and photobiology. B, Biology
• 作者: Conlon,KimberlyA;Berrios,Miguel
• 通讯作者: Berrios,Miguel