Cellular DNA is damaged in the course of normal cellular metabolic activities and by environmental factors such as chemicals and ultraviolet light that can cause DNA lesions. This DNA lesion damage is repaired by special translesion synthesis (TLS) DNA polymerases, Rev1 and PolZeta. Rev1 has deoxycytidine monophosphate (dCMP) transferase activity and functions as an insertion TLS polymerase, which incorporates nucleotides opposite damaged and non-damaged guanines. Rev1 recruits translesion polymerases and extender TLS polymerases, such as PolZeta. However, the interaction between Rev1 and Pol?? has remained unknown. We hypothesize some key residues that are involved in the Rev1-Pol?? interaction play an important role in DNA repair efficiency. The structural knowledge of the detailed structure of the Rev1-Pol?? complex will provide a mechanistic insight into the DNA repair and assist in drug design for cancer treatment. While our initial focus is on yeast Rev1-PolZeta, future studies will be done on the human system.