Influence of DNA structure on hypoxanthine and 1,N(6)-ethenoadenine removal by murine 3-methyladenine DNA glycosylase.
Influence of DNA structure on hypoxanthine and 1,N(6)-ethenoadenine removal by murine 3-methyladenine DNA glycosylase.
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DNA 结构对鼠 3-甲基腺嘌呤 DNA 糖基化酶去除次黄嘌呤和 1,N(6)-乙烯腺嘌呤的影响。
DOI：
10.1093/carcin/21.5.901
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发表时间：
2000
期刊：
影响因子：
4.7
通讯作者：
Samson,LD
中科院分区：
文献类型：
--
作者：
Wyatt,MD;Samson,LD
3-甲基腺嘌呤DNA糖基酶通过将含靶碱基的核苷酸从双链DNA翻转到活性部位口袋中，进行糖基键断裂和碱基释放，从而启动碱基切除修复。小鼠3-甲基腺嘌呤DNA糖基酶(3-甲基腺嘌呤除外)的底物碱基包括次黄嘌呤和1，N6-乙基腺嘌呤，这是两种由内源性和外源性因素形成的诱变加合物。利用特定碱基受损的双链DNA寡核苷酸，我们研究了这两种加合物在不同序列背景下的相对去除率。其中一个序列背景是A：T区，之所以选择A：T区，是因为已知DNA二级结构会随着该区长度的变化而改变，这是由于小槽的逐渐变窄。在这里，我们报告了次黄嘌呤的去除率，但对1，N6-乙烯腺嘌呤的去除率受其在A：T区的位置的显著影响。此外，还考察了当与胸腺嘧啶或胞嘧啶相反配对时，次黄嘌呤和1，N6-乙基腺嘌呤的清除率，并且在每个序列中，当相反胞嘧啶与胸腺嘧啶配对时，次黄嘌呤的清除率至少降低了20倍。相反，1，N6-乙基腺嘌呤的去除不受相反的嘧啶的身份的影响。我们的结论是，小鼠3-甲基腺嘌呤DNA糖基酶对某些碱基的去除可以受到相邻和相反序列上下文的调节。DNA序列背景对DNA修复率的影响，如本文所述，可能有助于在哺乳动物细胞中产生突变热点。
3-Methyladenine DNA glycosylases initiate base excision repair by flipping the nucleotide bearing the target base out of double-stranded DNA into an active site pocket for glycosylic bond cleavage and base release. Substrate bases for the murine 3-methyladenine DNA glycosylase (other than 3-methyladenine) include hypoxanthine and 1,N6-ethenoadenine, two mutagenic adducts formed by both endogenous and exogenous agents. Using double-stranded DNA oligonucleotides containing damaged bases at specific sites, we studied the relative removal rates for these two adducts when located in different sequence contexts. One of the sequence contexts was an A:T tract, chosen because DNA secondary structure is known to change along the length of this tract, due to a progressive narrowing of the minor groove. Here we report that removal rates for hypoxanthine, but not for 1,N6-ethenoadenine, are dramatically affected by its location within the A:T tract. In addition, the removal rates of hypoxanthine and 1,N6-ethenoadenine when paired opposite thymine or cytosine were examined, and in each sequence context hypoxanthine removal decreased by at least 20-fold when paired opposite cytosine versus thymine. In contrast, 1,N6-ethenoadenine removal was unaffected by the identity of the opposing pyrimidine. We conclude that the removal of certain bases by the mouse 3-methyladenine DNA glycosylase can be modulated by both adjacent and opposing sequence contexts. The influence of DNA sequence context upon DNA repair rates, such as those described here, may contribute to the creation of mutational hot spots in mammalian cells.
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影响因子：
11.4
作者：
OCONNOR, TR;LAVAL, F
通讯作者：
LAVAL, F
DOI：
10.1073/pnas.92.6.2204
发表时间：
1995-03
影响因子：
11.1
作者：
D. Wei;V. Maher;J. Mccormick
通讯作者：
D. Wei;V. Maher;J. Mccormick
影响因子：
14.9
作者：
CRUSE, WBT;AYMANI, J;LEONARD, GA
通讯作者：
LEONARD, GA
哪些结构特征决定了化学修饰 DNA 中修复酶的特异性和机制？
DOI：
10.1021/tx970011e
发表时间：
1997
期刊：
Chemical research in toxicology.
影响因子：
--
作者：
Singer,B;Hang,B
通讯作者：
Hang,B
人 3-甲基腺嘌呤-DNA 糖基化酶的纯化和表征。
影响因子：
14.9
作者：
Timothy R. O'Connor
通讯作者：
Timothy R. O'Connor