PDF(Pubmed)
Abstract：
Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/- mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER.
摘要：
转录对于细胞过程极为重要，但可能会受到RNA聚合酶II（RNAPII）暂停和停滞的阻碍。Cockayne综合征蛋白B（CSB）促进暂停的RNAPII的进展或启动转录偶联核苷酸切除修复（TC-NER）以去除停滞的RNAPII。然而,CSB在损伤后启动TC-NER的具体机制尚不清楚.在这项研究中,我们确定了ARK2N-CK2复合物在CSB介导的TC-NER启动中不可或缺的作用.ARK2N-CK2复合物通过CSB募集到损伤位点，然后磷酸化CSB。CSB的磷酸化增强了其与停滞的RNAPII的结合，延长CSB与染色质的关联并促进CSA介导的停滞RNAPII的泛素化。与这一发现一致，Ark2n-/-小鼠表现出类似于Cockayne综合征的表型。这些发现揭示了ARK2N-CK2复合物在通过CSB控制RNAPII命运中的关键作用，弥合启动TC-NER所需的关键差距。
