Abstract
Proliferating cell nuclear antigen (PCNA) is an essential protein that regulates the systematic recruitment and activity of proteins in a multitude of biochemical processes. Very few proteins, if any, bear similar responsibilities to those of PCNA, and its list of roles only continues to expand. However, even as one of the most well-studied proteins in research, many questions still remain about the complex quaternary structure and function of PCNA. Over the last forty years, we have gained a considerable amount of insight from studying amino acid substitutions within the protein. The combination of phenotypic and structural information about mutant PCNA proteins has shed light on the incredibly dynamic and accommodating nature of this important protein and why it stands at the crossroads of DNA metabolic pathways.