Nucleotide Excision Repair: Finely Tuned Molecular Orchestra of Early Pre-incision Events.
Nucleotide Excision Repair: Finely Tuned Molecular Orchestra of Early Pre-incision Events.
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DOI：
10.1111/php.12647
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发表时间：
2017-01
影响因子：
3.3
通讯作者：
Wani AA
中科院分区：
文献类型：
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作者：
Zhu Q;Wani AA
核苷酸切除修复（NER）消除了各种各样的螺旋扭曲DNA损伤，否则可能导致基因组不稳定。NER包括两个不同的子途径：在整个基因组中操作的全局基因组NER（GG-NER），以及优先从转录活性基因的转录DNA链中去除DNA损伤的转录偶联NER（TC-NER）。几种NER因子经历翻译后修饰，包括泛素化，在DNA损伤位点迅速且可逆地发生。越来越多的证据表明，泛素化不仅协调了时空招聘的关键蛋白质因子的DNA损伤位点，但也生产性组装NER切割前复合物。这篇综述将限于最新的概念性理解的泛素介导的调节初始损伤传感器的NER，即，DDB、XPC、RNAPII和CSB。我们项目假设NER模型中，泛素特异性分离酶，valosin-containing蛋白（VCP）/p97，在及时提取聚集的DNA损伤传感器功能上促进DNA损伤消除基因组中发挥着至关重要的作用。
Nucleotide excision repair (NER) eliminates a broad variety of helix-distorting DNA lesions that can otherwise cause genomic instability. NER comprises two distinct sub-pathways: global genomic NER (GG-NER) operating throughout the genome, and transcription-coupled NER (TC-NER) preferentially removing DNA lesions from transcribing DNA strands of transcriptionally active genes. Several NER factors undergo post-translational modifications, including ubiquitination, occurring swiftly and reversibly at DNA lesion sites. Accumulating evidence indicates that ubiquitination not only orchestrates the spatio-temporal recruitment of key protein factors to DNA lesion sites but also the productive assembly of NER preincision complex. This review will be restricted to the latest conceptual understanding of ubiquitin-mediated regulation of initial damage sensors of NER, i.e., DDB, XPC, RNAPII and CSB. We project hypothetical NER models in which ubiquitin-specific segregase, valosin-containing protein (VCP)/p97, plays an essential role in timely extraction of the congregated DNA damage sensors to functionally facilitate the DNA lesion elimination from the genome.