APOBEC3 Deaminases
The CCT chaperonin complex interacts with APOBEC3A and mitigates deaminase-induced DNA damage and cell death. We are investigating additional mechanisms by which the APOBEC3 enzymes are regulated in cancer and non-malignant cells.
The APOBEC3 deaminases are canonical innate immune effectors that act by mutating viral genomes leading to restriction of virus infection. When acting aberrantly, the APOBEC3 enzymes can deaminate, mutate, and damage the cellular genome. We are interested in the enzyme-intrinsic and enzyme-extrinsic factors that regulate APOBEC3 activity on virus and host DNA. For example, we found that the CCT chaperonin complex interacts with APOBEC3A and this interaction limits deamination-induced genotoxicity. As we uncover mechanisms by which APOBEC3 enzymes are regulated under normal conditions, we hope to determine how regulatory measures fail to enable APOBEC3 mutagenesis in human cancers. Using biochemical assays, immunoprecipitation, proteomics, and genome sequencing, we are investigating interactions of APOBEC3A with cellular processes and the genome.