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晶体结构和修复研究揭示了紫外线诱导的孢子光产物 DNA 损伤的身份和碱基配对性质。

Crystal structures and repair studies reveal the identity and the base-pairing properties of the UV-induced spore photoproduct DNA lesion.

机构信息

Center for Integrated Protein Science (CiPSM) at the Department of Chemistry, Ludwig-Maximilians-University, Munich, Germany.

出版信息

Chemistry. 2011 Aug 22;17(35):9651-7. doi: 10.1002/chem.201100177. Epub 2011 Jul 20.

Abstract

UV light is one of the major causes of DNA damage. In spore DNA, due to an unusual packing of the genetic material, a special spore photoproduct lesion (SP lesion) is formed, which is repaired by the enzyme spore photoproduct lyase (Spl), a radical S-adenosylmethionine (SAM) enzyme. We report here the synthesis and DNA incorporation of a DNA SP lesion analogue lacking the phosphodiester backbone. The oligonucleotides were used for repair studies and they were cocrystallized with a polymerase enzyme as a template to clarify the configuration of the SP lesion and to provide information about the base-pairing properties of the lesion. The structural analysis together with repair studies allowed us to clarify the identity of the preferentially repaired lesion diastereoisomer.

摘要

紫外线是造成 DNA 损伤的主要原因之一。在孢子 DNA 中,由于遗传物质的一种特殊包装方式,会形成一种特殊的孢子光产物损伤(SP 损伤),由酶孢子光产物裂合酶(Spl)修复,这是一种自由基 S-腺苷甲硫氨酸(SAM)酶。我们在此报告一种缺乏磷酸二酯骨架的 DNA SP 损伤类似物的合成和 DNA 掺入。这些寡核苷酸被用于修复研究,并与聚合酶一起结晶作为模板,以阐明 SP 损伤的结构,并提供有关损伤碱基配对性质的信息。结构分析与修复研究相结合,使我们能够阐明优先修复的损伤非对映异构体的身份。

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