Center for Integrated Protein Science (CiPSM) at the Department of Chemistry, Ludwig-Maximilians-University, Munich, Germany.
Chemistry. 2011 Aug 22;17(35):9651-7. doi: 10.1002/chem.201100177. Epub 2011 Jul 20.
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.
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。