DGCR8 regulates multiple processes of transcription coupled nucleotide excision repair.

Ultraviolet (UV) radiation is a major environmental factor that induces DNA lesions. Cells have evolved repair pathways, in which the transcription-coupled nucleotide excision repair (TC-NER) has a central role in removing the lesions. Here we demonstrate that DGCR8, known as a crucial component in microRNA biogenesis, coordinates the UV-induced formation of the TC-NER complex by interacting with TC-NER factors. These interactions could depend on the phosphorylation of Serine 153 of DGCR8, potentially serving as a functional switch from miRNA biogenesis to the TC-NER process. Interestingly, DGCR8 is also involved in recruiting chromatin remodelers, SPT16 and SMARCA5, for the TC-NER initiation, regulating UV-induced DNA/RNA hybrids (R-loops), and modulating DNA replication through the ATR-CHK1 checkpoint pathway. These findings reveal a novel essential regulator of TC-NER independently of miRNA processing and provide new insights into the relevant biological processes and pathological mechanisms.