The Snf2/Swi2 ATPase family of proteins is composed of different subfamilies with distinct functional roles, which can be classified based on the structure of their ATPase domains and other domains within the proteins. The Rad5/16 subfamily of Snf2/Swi2 ATPases is composed of Rad5 and Rad16, both of which play vital roles in different DNA repair pathways. Despite their activity in different repair pathways the structures of Rad5 and Rad16 are quite similar. Both contain the characteristic SNF2/SWI2 ATPase domains and, situated between the two ATPase domains, a Zinc-finger RING E3 ubiquitin ligase domain. Functionally, both Rad5 and Rad16 have ATPase activity, which is associated with chromatin remodeling to allow different proteins access to DNA, specifically at damaged sites. They also have E3 ubiquitin ligase activity, which is used to transfer ubiquitin molecules onto target substrates as a way of signaling for degradation or stability. The main difference between the two proteins is a characteristic HIRAN DNA binding domain, which is present at the N-terminus of Rad5, but absent in Rad16. Both proteins were initially discovered and characterized in Saccharomyces cerevisiae. Rad16 was demonstrated to be involved in nucleotide excision repair (NER), specifically global genome NER (ggNER). Rad5 was found to act in a variety of different instances, including: acting as a catalyst for translesion synthesis, acting in post replication repair as well as DNA double strand break (DSB) repair. Due to their roles, both proteins are extremely important as factors which help to enhance genome stability and promote ongoing genome integrity. Saccharomyces contains one constitutively silenced genomic locus, and since ggNER takes place in silenced areas of the genome this makes the study of ggNER proteins, such as Rad16, difficult. In contrast, Tetrahymena thermophila has a transcriptionally silent micronucleus, which provides a large platform for the study of Rad16 and ggNER. The goal of this work is to identify the homologs of both Rad16 and Rad5, while analyzing both their interactions and functions. Four putative homologs of Rad5/Rad16 were identified in Tetrahymena through bioinformatic analyses to elucidate sequence differences and similarities. Additionally, qRT-PCR analyses of homologs were conducted to determine expression in response to different DNA damaging agents; UV radiation to generate bulky adducts and induce NER, and methyl methanesulfonate (MMS) to induce DSB repair. To determine function in DNA repair and genomic integrity, shRNA constructs were created and transformed into cells to analyze the phenotypic consequences of decreased expression following UV and MMS damage.