ヒトヌクレチオド除去修復機構によって修復されるDNA酸化損傷とその生物学的意義 : 第12回公開シンポジウム : 活性酸素の分子病態学
スポンサーリンク
概要
- 論文の詳細を見る
Exposure of cellular DNA to reactive oxygen species generates several classes of base lesions, many of which are removed by the base excision-repair pathway. However, the lesions include purine cyclodeoxynucleoside formation by intramolecular cross-linking between the C-8 position of adenine or guanine and the 5' position of 2-deoxyribose. This distorting form of DNA damage, in which the purine is attached by two covalent bonds to the sugar-phosphate backbone, occurs as distinct diastereoisomers (R and S). It was observed here that both diastereoisomers block primer extension by mammalian and microbial replicative DNA polymerases, using DNA with a site-specific purine cyclodeoxynucleoside residue as template, and consequently appear to be cylotoxic lesions. The two forms of purine cyclodeoxynucleoside also interfered with digestion by 3'-5' exonuclease. Plasmid DNA containing either the 5'R or 5'S form of 5',8 cyclo-2-deoxyadenosine was a substrate for the human nucleotide excision-repair enzyme complex. The R isomer was more efficiently repaired than the S isomer. No correction of the lesion by direct damage reversal or base excision-repair was detected. Dual incision around the lesion was dependent on the core nucleotide excision-repair protein XPA. In contrast to several other types of oxidative DNA damage, purine cyclodeoxynucleosides are chemically stable and would be expected to accumulate at a slow rate over many years in the DNA of non-regenerating cells from xeroderma pigmentosum patients. High levels of this form of DNA damage may help explain the progressive neurodegeneration seen in XPA individuals.
- 日本環境変異原学会の論文
- 2001-12-22
著者
関連論文
- ヒトヌクレオチド除去修復機構によって除去されるサイクロプリン損傷
- ヒトヌクレチオド除去修復機構によって修復されるDNA酸化損傷とその生物学的意義 : 第12回公開シンポジウム : 活性酸素の分子病態学