Controlling Inflammation Through DNA Damage and Repair.
نویسندگان
چکیده
Advanced atherosclerotic plaques demonstrate extensive DNA damage, seen in smooth muscle cells, endothelial cells, macrophages and in circulating cells, and in both nuclei and mitochondria. DNA damage includes both singleor double-stranded breaks, deleted sections of DNA, nucleotide modifications, and extrusions of DNA from the nucleus (micronuclei). Reactive oxygen species (ROS) induce a variety of DNA damage, including oxidatively modified bases, apurinic/apyrimidinic sites, and strand breaks. Guanine is the most readily oxidized base, reacting with OH to generate a reducing neutral radical that reacts with O 2 , and via electron transfer, forms 8-oxo-7,8-dihydroguanine (8-oxo-G). 8-oxo-G and its products are the most abundant DNA lesions on oxidative exposure, with 1 to 2/10 residues in nuclear DNA and 1 to 3/10 residues in mitochondrial DNA (mtDNA), and up to 10 8-oxo-G lesions are formed in the cell daily. Advanced plaques are characterized by extensive accumulation of 8-oxo-G, seen in both macrophages and smooth muscle cells. 8-oxo-G is primarily repaired by base excision repair by several enzymes, including specific 8-oxo-G DNA glycosylases I and II (OGG1/2) and the Neilike (NEIL) glycosylases; the excised DNA is repaired by AP endonucleases before gap filling by polymerases and ligation.
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عنوان ژورنال:
- Circulation research
دوره 119 6 شماره
صفحات -
تاریخ انتشار 2016