Abasic Sites in the Transcribed Strand of Yeast DNA Are Removed by Transcription-Coupled Nucleotide Excision Repair
Abasic Sites in the Transcribed Strand of Yeast DNA Are Removed by Transcription-Coupled Nucleotide Excision Repair
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DOI：
10.1128/mcb.00308-10
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Jinks-Robertson, Sue
中科院分区：
文献类型：
--
作者：
Kim, Nayun;Jinks-Robertson, Sue
脱碱基（AP）位点是DNA和RNA聚合酶的有效阻断物，其修复对于维持基因组完整性至关重要。虽然AP位点通过碱基切除修复（BER）途径有效处理，但遗传研究表明修复也可以通过核苷酸切除修复（NER）发生。然而，NER参与AP部位切除一直令人困惑，因为该途径被认为仅针对大体积病变。在这里，我们研究了尿嘧啶从酵母中高度转录的基因中去除时产生的AP位点的修复。由于在这些条件下掺入尿嘧啶而不是胸腺嘧啶，因此所得AP位点的位置是已知的。结果表明，转录链上只有AP位点是NER的有效底物，这表明AP阻断的RNA聚合酶对NER机制的招募。AP位点的这种转录偶联NER可以解释先前提出的BER途径和转录之间的联系。
Abasic (AP) sites are potent blocks to DNA and RNA polymerases, and their repair is essential for maintaining genome integrity. Although AP sites are efficiently dealt with through the base excision repair (BER) pathway, genetic studies suggest that repair also can occur via nucleotide excision repair (NER). The involvement of NER in AP-site removal has been puzzling, however, as this pathway is thought to target only bulky lesions. Here, we examine the repair of AP sites generated when uracil is removed from a highly transcribed gene in yeast. Because uracil is incorporated instead of thymine under these conditions, the position of the resulting AP site is known. Results demonstrate that only AP sites on the transcribed strand are efficient substrates for NER, suggesting the recruitment of the NER machinery by an AP-blocked RNA polymerase. Such transcription-coupled NER of AP sites may explain previously suggested links between the BER pathway and transcription.