TL;DR
This review comprehensively summarizes the structural and functional roles of the CPSF complex in cancer biology and targeted therapy, and explores its emerging function as a guardian of genomic stability.
The human genome encodes several hundreds of ubiquitin E3 enzymes, most of which have poorly understood biological roles. In search for novel ubiquitin E3 enzymes involved in DNA damage tolerance, we identified RNF25 as a candidate to have a role in DNA replication stress tolerance. Under stress conditions, RNF25 trans...
It is shown that primary tumor cells depend on high CPSF73 and PCF11 levels, whereas metastatic cells are less sensitive, and the distance between 3' cleavage and termination is nearly halved in primary tumor cells compared with normal cells and becomes particularly short in oncogenes.
These findings establish ECAS as a chromatin-associated assembly that couples productive elongation with RNA processing and establishes Aqr as a highly expressed cell that profoundly impairs leukemia initiation, maintenance, and leukemia stem cell function in MLL-rearranged leukemia.
This review focuses on the emerging roles of BRCA2 in transcription-related pathways, including R-loop homeostasis, resolution of transcription-replication conflicts, RNA polymerase II dynamics, and broader transcriptional regulation.
Maintenance of genome integrity requires accurate repair of DNA double-strand breaks (DSBs), particularly within transcriptionally active regions. Persistent R-loops at DSBs can impede homologous recombination (HR) repair. While factors that resolve R-loops at DSB sites are known, the mechanisms ensuring timely degrada...
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