Def1 and Dst1 play distinct roles in repair of AP lesions in highly transcribed genomic regions.
Def1 and Dst1 play distinct roles in repair of AP lesions in highly transcribed genomic regions.
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DOI：
10.1016/j.dnarep.2017.05.003
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发表时间：
2017-07
期刊：
影响因子：
3.8
通讯作者：
Kim N
中科院分区：
文献类型：
--
作者：
Owiti N;Lopez C;Singh S;Stephenson A;Kim N
自发性DNA损伤产生的碱基位点或AP位点在酿酒酵母基因组的活性转录区以更高的速率积累，并主要通过碱基切除修复（BER）途径修复。我们已经证明转录偶联核苷酸切除修复（NER）途径可以在功能上取代BER修复位于转录链上的AP位点，就像紫外线诱导的嘧啶二聚体的链特异性修复一样。先前的报道表明，转录修复偶联因子CSB的酵母同源物Rad26在一定程度上介导了uv -二聚体和AP损伤的链特异性修复。在这里，我们报道了Def1，已知可以促进泛素化和停滞RNA聚合酶复合物的降解，也可以将NER引导到活跃转录基因转录链上的AP病变，但其功能依赖于酵母细胞的代谢状态。我们还发现Dst1是哺乳动物转录延伸因子TFIIS的同系物，它在抑制同源重组途径的同时干扰ner依赖性AP损伤的修复。总的来说，Def1和Dst1介导ap诱导的转录停滞的结果非常不同。
Abasic or AP sites generated by spontaneous DNA damage accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) pathway. We have demonstrated that transcription-coupled nucleotide excision repair (NER) pathway can functionally replace BER to repair those AP sites located on the transcribed strand much like the strand specific repair of UV-induced pyrimidine dimers. Previous reports indicate that Rad26, a yeast homolog of transcription-repair coupling factor CSB, partly mediates strand-specific repair of UV-dimers as well as AP lesions. Here, we report that Def1, known to promote ubiquitination and degradation of stalled RNA polymerase complex, also directs NER to AP lesions on the transcribed strand of an actively transcribed gene but that its function is dependent on metabolic state of the yeast cells. We additionally show that Dst1, a homolog of mammalian transcription elongation factor TFIIS, interferes with NER-dependent repair of AP lesions while suppressing homologous recombination pathway. Overall, Def1 and Dst1 mediate very different outcomes in response to AP-induced transcription arrest.
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