Sunesen Morten, Stevnsner Tinna, Brosh Robert M, Dianov Grigory L, Bohr Vilhelm A
Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.
Oncogene. 2002 May 16;21(22):3571-8. doi: 10.1038/sj.onc.1205443.
Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo.
科凯恩综合征（CS）是一种常染色体隐性人类疾病，其特征为对紫外线敏感以及存在神经和发育异常。现已确定了两个互补组，分别命名为CS - A和CS - B。传统上，CSA和CSB在核苷酸切除修复（NER）的转录偶联修复（TCR）途径中发挥作用，该途径可有效从RNA聚合酶II转录基因的转录链中去除大的损伤。为了评估CSB蛋白在修复高致突变性碱基损伤7,8 - 二氢 - 8 - 氧代鸟嘌呤（8 - oxoG）中的作用，我们使用细胞提取物通过体外切口方法以及采用基因特异性修复测定的改良方案的体内方法来研究该损伤的去除情况，该改良方案可测量基因组内序列中的碱基损伤修复。我们的结果表明，CSB蛋白的完整性对于导致在8 - oxoG位点进行切口的过程至关重要，并且该损伤的全基因组修复（GGR）在体内需要功能性的CSB基因产物。
