The mutagenicity of thymidine glycol in Escherichia coli is increased when it is part of a tandem lesion.
The mutagenicity of thymidine glycol in Escherichia coli is increased when it is part of a tandem lesion.
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DOI：
10.1021/bi900927d
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Greenberg, Marc M.
中科院分区：
文献类型：
--
作者：
Huang, Haidong;Imoto, Shuhei;Greenberg, Marc M.
串联损伤由两个连续受损的核苷酸组成。串联损伤是由嘧啶核碱基自由基产生的反应产物的主要家族，其通过电离辐射大量形成。其中一个串联病变包含胸苷二醇病变，其5 ′侧为2-脱氧核糖内酯（LTg）。在E.大肠杆菌中使用单链基因组。LTg是比胸苷乙二醇更有效的复制阻断剂，并且仅在SOS诱导的条件下被绕过。在野生型细胞中，相邻的胸苷二醇并不显著影响与2-脱氧核糖酸内酯相反的核苷酸掺入。相比之下，当LTg侧翼为3 '-dG时，野生型细胞中胸苷二醇相对的错误插入频率（在不存在2-脱氧核糖内酯的情况下可以忽略不计）增加至10%。侧翼核苷酸不同且在缺乏SOS诱导的旁路聚合酶之一的细胞中进行的实验表明，突变是由于引物在绕过病变之前错位的机制造成的，这使得额外的核苷酸可以掺入3 '侧翼核苷酸。随后的重新排列和延伸导致观察到的突变。DNA聚合酶II和IV负责错位诱导的突变，并与DNA聚合酶V竞争，后者通过串联损伤读取。这些实验表明，将胸苷二醇掺入串联损伤中通过阻断复制间接诱导突变增加，这使得错位-重新排列机制能够与Pol V的直接旁路竞争。
Tandem lesions are comprised of two contiguously damaged nucleotides. Tandem lesions are the major family of reaction products generated from a pyrimidine nucleobase radical, which are formed in large amounts by ionizing radiation. One of these tandem lesions contains a thymidine glycol lesion flanked on its 5′-side by 2-deoxyribonolactone (LTg). The replication of this tandem lesion was investigated in E. coli using single stranded genomes. LTg is a much more potent replication block than thymidine glycol and is bypassed only under SOS-induced conditions. The adjacent thymidine glycol does not significantly affect nucleotide incorporation opposite 2-deoxyribonolactone in wild type cells. In contrast, the misinsertion frequency opposite thymidine glycol, which is negligible in the absence of 2-deoxyribonolactone increases to 10% in wild type cells when LTg is flanked by a 3′-dG. Experiments in which the flanking nucleotides are varied and in cells lacking one of the SOS-induced bypass polymerases indicate that the mutations are due to a mechanism in which the primer misaligns prior to bypassing the lesion, which allows for an additional nucleotide to be incorporated across from the 3′-flanking nucleotide. Subsequent realignment and extension results in the observed mutations. DNA polymerases II and IV are responsible for misalignment induced mutations, and compete with DNA polymerase V which reads through the tandem lesion. These experiments reveal that incorporation of the thymidine glycol into a tandem lesion indirectly induces increases in mutations by blocking replication, which enables the misalignment-realignment mechanism to compete with direct bypass by Pol V.
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影响因子：
2.9
作者：
Colis, Laureen C.;Raychaudhury, Paromita;Basu, Ashis K.
通讯作者：
Basu, Ashis K.
DOI：
10.1073/pnas.131077798
发表时间：
2001-06-19
影响因子：
11.1
作者：
Blaisdell, JO;Wallace, SS
通讯作者：
Wallace, SS
影响因子：
15
作者：
Carter, KN;Greenberg, MM
通讯作者：
Greenberg, MM
影响因子：
3.5
作者：
Carter, KN;Greenberg, MM
通讯作者：
Greenberg, MM
影响因子：
3.4
作者：
Hada, M;Sutherland, BM
通讯作者：
Sutherland, BM