Heterogeneous repair of N-methylpurines at the nucleotide level in normal human cells.
Heterogeneous repair of N-methylpurines at the nucleotide level in normal human cells.
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正常人体细胞中核苷酸水平 N-甲基嘌呤的异质修复。
DOI：
10.1006/jmbi.1998.2138
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发表时间：
1998
影响因子：
5.6
通讯作者：
O'Connor,TR
中科院分区：
文献类型：
--
作者：
Ye,N;Holmquist,GP;O'Connor,TR
硫酸二甲酯诱导的3-甲基腺嘌呤和7-甲基鸟嘌呤加合物的碱基切除修复率在正常人成纤维细胞中沿PGK 1基因的核苷酸分辨率沿着测量。7-甲基鸟嘌呤的修复率显示了30倍的核苷酸位置依赖性，而3-甲基腺嘌呤的位置依赖性修复率变化只有6倍。缓慢的切除率为7-甲基鸟嘌呤基地提供了机会，研究他们的切除在体外作为一个模型的基础切除修复。由人N-甲基嘌呤-DNA糖基化酶（MPG蛋白）和硫酸二甲酯损伤的DNA组成的双组分体外切除系统表现出7-甲基鸟嘌呤从位置到位置高达185倍的序列上下文依赖性速率差异。这种体外系统再现了整体修复率，以及PGK 1编码区，在细胞中观察到的位置依赖性修复模式。体内修复和体外切除数据的等效性表明，通过MPG蛋白去除7-甲基鸟嘌呤是该病变的碱基切除修复中的限速步骤。与DNA糖基化酶可及性相关的DNA“修复率足迹”仅在结合转录因子的区域中观察到。“修复率足迹”代表7-meG碱基切除修复的罕见染色质组分，否则由序列上下文依赖性主导。然而，3-甲基腺嘌呤的体内修复率与体外修复率的比较表明，决定这种加合物的位置依赖性修复的限速步骤是在DNA糖基化酶后阶段之一。总之，本研究表明，序列上下文依赖性体外反应率与体内位置依赖性修复率的比较允许识别负责位置依赖性修复的步骤。这种分析现在对于通过碱基切除修复途径修复的不同步骤和加合物是可行的。
Base excision repair rates of dimethyl sulfate-induced 3-methyladenine and 7-methylguanine adducts were measured at nucleotide resolution along the PGK1 gene in normal human fibroblasts. Rates of 7-methylguanine repair showed a 30-fold dependence on nucleotide position, while position-dependent repair rates of 3-methyladenine varied only sixfold. Slow excision rates for 7-methylguanine bases afforded the opportunity to study their excision in vitro as a model for base excision repair. A two-component in vitro excision system, composed of human N-methylpurine-DNA glycosylase (MPG protein) and dimethyl sulfate-damaged DNA manifested sequence context-dependent rate differences for 7-methylguanine of up to 185-fold from position to position. This in vitro system reproduced both the global repair rate, and for the PGK1 coding region, the position-dependent repair patterns observed in cells. The equivalence of in vivo repair and in vitro excision data indicates that removal of 7-methylguanine by the MPG protein is the rate-limiting step in base excision repair of this lesion. DNA “repair rate footprints” associated with DNA glycosylase accessibility were observed only in a region with bound transcription factors. The “repair rate footprints” represent a rare chromatin component of 7-meG base excision repair otherwise dominated by sequence-context dependence. Comparison of in vivo repair rates to in vitro rates for 3-methyladenine, however, shows that the rate-limiting step determining position-dependent repair for this adduct is at one of the post-DNA glycosylase stages. In conclusion, this study demonstrates that a comparison of sequence context-dependent in vitro reaction rates to in vivo position-dependent repair rates permits the identification of steps responsible for position-dependent repair. Such analysis is now feasible for the different steps and adducts repaired via the base excision repair pathway.
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影响因子：
11.4
作者：
OCONNOR, TR;LAVAL, F
通讯作者：
LAVAL, F
从人类细胞中受损的 DNA 中酶促释放 5-末端脱氧核糖磷酸残基。
影响因子：
2.9
作者：
A. Price;T. Lindahl
通讯作者：
T. Lindahl
人 X 连锁 3-磷酸甘油酸激酶基因启动子区域的序列。
影响因子：
3.5
作者：
J. Singer;Douglas H. Keith;Kenzaburo Tani;Robert L. Simmer;Louise Shively;Susan Lindsay;Akira Yoshida;Arthur D. Riggs
通讯作者：
Arthur D. Riggs
核酸-蛋白质复合物的足迹
影响因子：
5.6
作者：
A. Revzin
通讯作者：
A. Revzin
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