Greehey CCRI Fall ’26 Seminar Series: Reuben Harris, PhD (UTHSA)
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Greehey Children's Cancer Research Institute
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Mutations are required for cancer development and progression. DNA cytosine deaminase enzymes called APOBECs function normally to prevent viral infections. However, these enzymes often become dysregulated in cancer and deaminate cytosines-to-uracils (C-to-U) in chromosomal DNA, resulting in mutations, DNA breakage, and larger-scale aberrations such as insertions/deletions and translocations. In fact, APOBEC mutagenesis impacts 70% of all cancer types and is by far the dominant mutagen in many. Accordingly, APOBEC mutagenesis associates with detrimental clinical outcomes, including tumor development, drug resistance, and metastasis, and has become a novel drug target. This seminar will summarize recent progress in this exciting area including the discovery of an unexpected mutational synergy between DNA adducting carcinogens and APOBEC deamination activity.