Abstract 1054 Determining the PRMT5-RuvBL1 heteromeric complex and its role in DNA repair

Cancer has remained a leading cause of death for over 75 years.Cancer is characterized by genomic instability comprising deletions and mutations that can affect proteins crucial for cell regulation.PRMT5, a member of the protein-arginine methyltransferase (PRMT) family of proteins, has shown significance in regulating many cancers by serving as an epigenetic regulator.PRMT5 methylates RuvBL1, which promotes homologous recombination (HR)-mediated DSB repair by promoting histone acetylation, allowing for the removal of histones and proper repair of damaged DNA.Studies have shown that knockdown of PRMT5 in yeast (Skb1) leads to more intrachromosomal deletions (ICDs) following doublestrand breaks.These findings suggest that PRMT5 aids in error-free DSB repair and in its absence, there is an increase in error-prone repair.Despite current developments, research continues to lack proper understanding of how PRMT5 is involved in regulating various DSB repair pathways.However, its potential to prevent further development of many cancers influences many researchers to focus on understanding it.Through computational experimentation, our work aims to expand concurrent understanding of PRMT5's involvement in transforming cells into cancer.Computational modeling was performed on both the human and yeast homologs of PRMT5 (Skb1 in yeast) and RuvBL1 (Rvb1 in yeast) using proteinprotein docking web servers such as ZDock and HDock.The modeled complexes were aligned in PyMOL to identify similar models and determine the most common amino acids involved at the interface.The high structural similarity between the yeast and human proteins suggests a homologous interaction, allowing us to translate our results between species.Cancerassociated mutations in PRMT5 and RuvBL1 using the COS-MIC database were analyzed and mapped onto the modeled protein complexes to understand their impact on protein function and structure.