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大肠杆菌OGT对O6-2'-脱氧鸟苷加合物的合成、生物物理及修复研究

Synthesis, biophysical and repair studies of O6-2'-deoxyguanosine adducts by Escherichia coli OGT.

作者信息

Schoonhoven Nadia M, Murphy Sebastian P, O'Flaherty Derek K, Noronha Anne M, Kornblatt M Judith, Wilds Christopher J

机构信息

Department of Chemistry & Biochemistry, Concordia University, 7141 Sherbooke St. West, Montreal, Canada.

出版信息

Nucleic Acids Symp Ser (Oxf). 2008(52):449-50. doi: 10.1093/nass/nrn228.

DOI:10.1093/nass/nrn228
PMID:18776447
Abstract

Oligonucleotides containing modified 2'-deoxyguanosines bearing a seven carbon linker at the O(6)- atom with either a terminal hydroxyl or 2'- deoxyguanosine group have been synthesized as potential intermediates formed during repair of interstrand cross-linked DNA. Repair of these substrates with Escherichia coli OGT was investigated with an assay involving cleavage of the unmodified duplex with the restriction endonuclease PvuII followed by analysis of the products by denaturing polyacrylamide gel electrophoresis. Duplexes containing these modifications were repaired by OGT suggesting that direct repair may play a role, in combination with other repair pathways, in reversing interstrand crosslink DNA damage.

摘要

已合成了含有修饰的2'-脱氧鸟苷的寡核苷酸,这些2'-脱氧鸟苷在O(6)原子处带有一个七碳连接子,其末端为羟基或2'-脱氧鸟苷基团,作为链间交联DNA修复过程中形成的潜在中间体。用大肠杆菌OGT对这些底物进行修复的研究采用了一种分析方法,该方法包括用限制性内切酶PvuII切割未修饰的双链体,然后通过变性聚丙烯酰胺凝胶电泳分析产物。含有这些修饰的双链体可被OGT修复,这表明直接修复可能与其他修复途径一起,在逆转链间交联DNA损伤中发挥作用。

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