Genome stability is fundamental for maintaining cellular function, relying on accurate DNA replication, repair systems, chromosome segregation, and chromatin structure. Moreover, epigenetic modifications such as histone ubiquitination play a pivotal role in regulating RNA Polymerase II-driven transcription and the DNA damage response (DDR). Our research focuses on the kinases CDK12 and CDK13, exploring their expanded roles in transcriptional regulation. Phosphoproteomic analysis of CDK12/CDK13-inhibited cell lines were conducted to find additional phosphosites besides Serin-2 the C-terminal domain of RNA Polymerase II. Remarkably, two major phosphosites in the CDK13-inhibited cell line were altered belonging to a protein interactor called WAC (WW-containing adaptor protein with coiled-coil). During transcriptional elongation, WAC interacts with phosphorylated C-terminal domain of RNA Pol II via its WW domain and attracts via its coiled-coil domain the ubiquitination machinery (RNF20/40) to the chromatin. Changes in RNF20/40 or WAC activity are examples of functional perturbations in this pathway that affect transcription, DNA repair, and differentiation. These changes have implications for the advancement of cancer and neurodevelopmental diseases such as De-Santo Shinawi Syndrome. More research is needed to determine the RNF20/40/WAC complex's functional importance and molecular mechanism. By guaranteeing a full stage of elongation during RNA Pol II-mediated transcription and its function to assure DNA damage repair under genotoxic stress, we clearly wish to demonstrate the significant role that this complex plays. This initiative aims to investigate the biology of WAC, which appears to be controlled by CDK13. The location and timing of the WAC-mediated ubiquitination of H2B in actively transcribed genes are what we are trying to determine by using advanced genomics and structural biology methods.