STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

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. As the major pathway to deal with transcription-blocking lesions, the mechanism and critical factors of mammalian transcription-coupled repair (TCR) remain poorly understood since its discovery nearly 40 years ago. In this study, the authors demonstrate that serine/threonine kinase 19 (STK19) is an essential TCR factor in human cells. STK19 directly interacts with RNA polymerase II, CSA and TFIIH, and is recruited to damage sites after CSA. Furthermore, it supports TCR by stimulating UVSSA ubiquitination and TFIIH loading. As a new fundamental TCR factor that is not a component of the transcription elongation complex, research on STK19 will help complete a crucial piece of the puzzle in understanding the molecular mechanism of human TCR. Graphical Abstract