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Transcription-Coupled DNA Repair: From Mechanism to Human Disorder
Trends in Cell Biology ( IF 13.0 ) Pub Date : 2021-03-05 , DOI: 10.1016/j.tcb.2021.02.007
Diana van den Heuvel 1 , Yana van der Weegen 1 , Daphne E C Boer 1 , Tomoo Ogi 2 , Martijn S Luijsterburg 1
Affiliation  

DNA lesions pose a major obstacle during gene transcription by RNA polymerase II (RNAPII) enzymes. The transcription-coupled DNA repair (TCR) pathway eliminates such DNA lesions. Inherited defects in TCR cause severe clinical syndromes, including Cockayne syndrome (CS). The molecular mechanism of TCR and the molecular origin of CS have long remained enigmatic. Here we explore new advances in our understanding of how TCR complexes assemble through cooperative interactions between repair factors stimulated by RNAPII ubiquitylation. Mounting evidence suggests that RNAPII ubiquitylation activates TCR complex assembly during repair and, in parallel, promotes processing and degradation of RNAPII to prevent prolonged stalling. The fate of stalled RNAPII is therefore emerging as a crucial link between TCR and associated human diseases.



中文翻译:

转录偶联 DNA 修复:从机制到人类疾病

DNA 损伤在 RNA 聚合酶 II (RNAPII) 酶的基因转录过程中构成主要障碍。转录偶联 DNA 修复 (TCR) 途径消除了此类 DNA 损伤。TCR 的遗传缺陷会导致严重的临床综合征,包括 Cockayne 综合征 (CS)。TCR 的分子机制和 CS 的分子起源长期以来一直是个谜。在这里,我们探索了我们对 TCR 复合物如何通过由 RNAPII 泛素化刺激的修复因子之间的协同相互作用进行组装的新进展。越来越多的证据表明,RNAPII 泛素化在修复过程中会激活 TCR 复合物组装,同时促进 RNAPII 的加工和降解,以防止长时间停滞。因此,停滞的 RNAPII 的命运正在成为 TCR 与相关人类疾病之间的关键联系。

更新日期:2021-04-15
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