GSE201158
Ubiquitin ligase TRAIP plays an essential role during the S-phase of unperturbed cell cycle in the resolution of DNA replication – transcription conflicts
Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. TRAIP E3 ubiquitin ligase has been shown over the years to play a role in a number of the cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, for the first time we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We found that upon rapid TRAIP degradation cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. TRAIP degradation in specific stages of the cell cycle revealed that TRAIP plays its essential role in S-phase and that the lack of TRAIP results in the generation of DNA damage at transcription start sites due to replication-transcription collisions. Overall design: Identification of hotspots of DNA damage following the removal of TRAIP by auxin-induced degradation