MsDpo4-a DinB Homolog from Mycobacterium smegmatis-Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches.

MsDpo4-a DinB Homolog from Mycobacterium smegmatis-Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches.
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DOI:
10.1155/2012/285481
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发表时间:
2012
影响因子:
2.3
通讯作者:
Nair DT
Nair DT
中科院分区:
其他
文献类型:
--
作者:
Sharma A;Nair DT

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原核生物中容易出错的DNA合成赋予基因组可塑性,以允许在不利的环境条件下进化,这种现象被称为适应性突变。在分子水平上,适应性诱变通过上调通常属于Y家族的特化易错DNA聚合酶的表达来介导,例如在大肠杆菌的情况下dinB基因的多肽产物。杆菌然而,与E.在大肠杆菌中,已经发现在应激条件下,结核分枝杆菌中dinB同源物的表达不上调。这些研究表明,分枝杆菌中的DinB同源物可能无法促进错配并参与适应性诱变。我们表明,从耻垢分枝杆菌(MsDpo4)的代表性同源物可以进行模板依赖性的核苷酸掺入,因此是一种DNA聚合酶。此外,可以看出MsDpo 4也能够错误掺入,具有促进G:T和T:G错配的显著能力。这两种错配的错误掺入频率与古细菌和原核同源物所表现出的频率相似。总的来说,我们的数据表明MsDpo4有能力促进过渡突变,并可能赋予基因组可塑性。
Error-prone DNA synthesis in prokaryotes imparts plasticity to the genome to allow for evolution in unfavorable environmental conditions, and this phenomenon is termed adaptive mutagenesis. At a molecular level, adaptive mutagenesis is mediated by upregulating the expression of specialized error-prone DNA polymerases that generally belong to the Y-family, such as the polypeptide product of the dinB gene in case of E. coli. However, unlike E. coli, it has been seen that expression of the homologs of dinB in Mycobacterium tuberculosis are not upregulated under conditions of stress. These studies suggest that DinB homologs in Mycobacteria might not be able to promote mismatches and participate in adaptive mutagenesis. We show that a representative homolog from Mycobacterium smegmatis (MsDpo4) can carry out template-dependent nucleotide incorporation and therefore is a DNA polymerase. In addition, it is seen that MsDpo4 is also capable of misincorporation with a significant ability to promote G:T and T:G mismatches. The frequency of misincorporation for these two mismatches is similar to that exhibited by archaeal and prokaryotic homologs. Overall, our data show that MsDpo4 has the capacity to facilitate transition mutations and can potentially impart plasticity to the genome.