Replication of O6-Methylguanine-containing DNA by Repair and Replicative DNA Polymerases*
Replication of O6-Methylguanine-containing DNA by Repair and Replicative DNA Polymerases*
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通过修复和复制 DNA 聚合酶复制含 O6-甲基鸟嘌呤的 DNA*
DOI：
10.1074/jbc.271.33.20088
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Samuel H. Wilson
中科院分区：
文献类型：
--
作者：
L. Reha;R. Nonay;R. Day;Samuel H. Wilson
DNA中o6 -甲基鸟嘌呤（m6G）的生物学后果已经得到了很好的认识。当模板m6G遇到DNA聚合酶时，复制受到阻碍，而跨损伤复制导致与模板m6G相反的dTMP优先掺入。因此，DNA中未修复的m6G具有细胞毒性和诱变性。然而，已经分离出耐m6G的细胞系，这表明一些细胞DNA聚合酶可以以合理的效率复制含m6G的DNA。先前的报道认为哺乳动物pol β不能复制含有m6g的DNA，但我们发现pol β可以催化跨损伤复制；然而，病变必须存在于pol β活性，单核苷酸或短核苷酸缺口底物的最佳环境中。据早期研究报道，带或不带模板m6G的引物单链DNA模板是pol β的不良底物。相比之下，通过噬菌体T4 DNA聚合酶观察到对引物单链DNA模板的跨病灶复制。T4 DNA聚合酶复制含m6g的DNA需要gp45辅助蛋白将聚合酶夹在DNA模板上。通过测试的两种DNA聚合酶复制含m6g的DNA的限速步骤是从病变处加入dTMP。
The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol β could not replicate m6G-containing DNA, but we find that pol β can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol β activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol β as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.
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体外 DNA 复制过程中模板 DNA 中 O6-甲基鸟嘌呤的碱基配对特性。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Snow,ET;Foote,RS;Mitra,S
通讯作者：
Mitra,S
DOI：
10.1016/s0021-9258(19)49692-0
发表时间：
1992-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Reddy;S. Weitzel;P. V. Hippel
通讯作者：
M. Reddy;S. Weitzel;P. V. Hippel
O6-甲基鸟嘌呤切口：人体细胞提取物导致 DNA 中胸腺嘧啶错配。
影响因子：
2.9
作者：
Sibghat-Ullah;Day3rd,RS
通讯作者：
Day3rd,RS
DOI：
10.1073/pnas.90.14.6424
发表时间：
1993-07-15
影响因子：
11.1
作者：
KAT, A;THILLY, WG;MODRICH, P
通讯作者：
MODRICH, P
DOI：
10.1073/pnas.81.20.6271
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LOECHLER, EL;GREEN, CL;ESSIGMANN, JM
通讯作者：
ESSIGMANN, JM