Yuanqing Tan, Meng Gao, Yanchao Huang, Delin Zhan, Sizhong Wu, Jiao An, Xiping Zhang, Jinchuan Hu
{"title":"STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading","authors":"Yuanqing Tan, Meng Gao, Yanchao Huang, Delin Zhan, Sizhong Wu, Jiao An, Xiping Zhang, Jinchuan Hu","doi":"10.1093/nar/gkae787","DOIUrl":null,"url":null,"abstract":"Transcription-coupled repair (TCR) is the major pathway to remove transcription-blocking lesions. Although discovered for nearly 40 years, the mechanism and critical players of mammalian TCR remain unclear. STK19 is a factor affecting cell survival and recovery of RNA synthesis in response to DNA damage, however, whether it is a necessary component for TCR is unknown. Here, we demonstrated that STK19 is essential for human TCR. Mechanistically, STK19 is recruited to damage sites through direct interaction with CSA. It can also interact with RNA polymerase II in vitro. Once recruited, STK19 plays an important role in UVSSA ubiquitination which is needed for TCR. STK19 also promotes TCR independent of UVSSA ubiquitination by stimulating TFIIH recruitment through its direct interaction with TFIIH. In summary, our results suggest that STK19 is a key factor of human TCR that links CSA, UVSSA ubiquitination and TFIIH loading, shedding light on the molecular mechanisms of TCR.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":null,"pages":null},"PeriodicalIF":16.6000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleic Acids Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/nar/gkae787","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Transcription-coupled repair (TCR) is the major pathway to remove transcription-blocking lesions. Although discovered for nearly 40 years, the mechanism and critical players of mammalian TCR remain unclear. STK19 is a factor affecting cell survival and recovery of RNA synthesis in response to DNA damage, however, whether it is a necessary component for TCR is unknown. Here, we demonstrated that STK19 is essential for human TCR. Mechanistically, STK19 is recruited to damage sites through direct interaction with CSA. It can also interact with RNA polymerase II in vitro. Once recruited, STK19 plays an important role in UVSSA ubiquitination which is needed for TCR. STK19 also promotes TCR independent of UVSSA ubiquitination by stimulating TFIIH recruitment through its direct interaction with TFIIH. In summary, our results suggest that STK19 is a key factor of human TCR that links CSA, UVSSA ubiquitination and TFIIH loading, shedding light on the molecular mechanisms of TCR.
期刊介绍:
Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.