Processing of thymine glycol in a clustered DNA damage site: mutagenic or cytotoxic
نویسندگان
چکیده
منابع مشابه
Processing of thymine glycol in a clustered DNA damage site: mutagenic or cytotoxic
Localized clustering of damage is a hallmark of certain DNA-damaging agents, particularly ionizing radiation. The potential for genetic change arising from the effects of clustered damage sites containing combinations of AP sites, 8-oxo-7,8-dihydroguanine (8-oxoG) or 5,6-dihydrothymine is high. To date clusters containing a DNA base lesion that is a strong block to replicative polymerases, have...
متن کاملEnhanced mutagenic potential of 8-oxo-7,8-dihydroguanine when present within a clustered DNA damage site.
The formation of clustered DNA damage sites is a unique feature of ionizing radiation. Recent studies have shown that the repair of lesions within clusters may be compromised, but little is understood about the mutagenic consequences of such damage sites. Using a plasmid-based method, damaged DNA containing uracil positioned at 1-5 bp separations from 8-oxo-7,8-dihydroguanine on the complementa...
متن کاملThymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage.
Thymine glycol is a DNA damage product of ionizing radiation and other oxidative mutagens. In an attempt to find a noninvasive assay for oxidative DNA damage in individuals, we have developed an HPLC assay for free thymine glycol and thymidine glycol in urine. Our results indicate that humans excrete about 32 nmol of the two glycols per day. Rats, which have a higher specific metabolic rate and...
متن کاملThe roles of specific glycosylases in determining the mutagenic consequences of clustered DNA base damage
The potential for genetic change arising from specific single types of DNA lesion has been thoroughly explored, but much less is known about the mutagenic effects of DNA lesions present in clustered damage sites. Localized clustering of damage is a hallmark of certain DNA-damaging agents, particularly ionizing radiation. We have investigated the potential of a non-mutagenic DNA base lesion, 5,6...
متن کاملPreferential formation of (5S,6R)-thymine glycol for oligodeoxyribonucleotide synthesis and analysis of drug binding to thymine glycol-containing DNA
We previously reported the chemical synthesis of oligonucleotides containing thymine glycol, a major form of oxidative DNA damage. In the preparation of the phosphoramidite building block, the predominant product of the osmium tetroxide oxidation of protected thymidine was (5R,6S)-thymidine glycol. To obtain the building block of the other isomer, (5S,6R)-thymidine glycol, in an amount sufficie...
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ژورنال
عنوان ژورنال: Nucleic Acids Research
سال: 2009
ISSN: 0305-1048,1362-4962
DOI: 10.1093/nar/gkp422