학술논문
The ARK2N-CK2 complex initiates transcription-coupled repair through enhancing the interaction of CSB with lesion-stalled RNAPII.
Document Type
Academic Journal
Author
Luo Y; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Li J; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Li X; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Lin H; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Mao Z; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Xu Z; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Li S; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Nie C; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Zhou XA; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Liao J; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Xiong Y; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Xu X; Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518055, China.; Wang J; Department of Radiation Medicine, School of Basic Medical Sciences, Peking University International Cancer Institute, Institute of Advanced Clinical Medicine, State Key Laboratory of Molecular Oncology, Peking University Health Science Center, Beijing 100191, China.; Department of Gastrointestinal Translational Research, Peking University Cancer Hospital, Beijing 100142, China.
Source
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Competing Interests: Competing interests statement:The authors declare no competing interest.