Mutagenic Deaminase Activity in Cancer
Abstract
The APOBEC3 family of enzymes are encoded by the cellular genome and function in the innate immune response to viral infection. By catalyzing the conversion of cytidine to uracil in DNA substrates, APOBEC3 enzymes mutate viral genomes and limit replication, progeny production, and infection. However, the APOBEC3A family member is a potent deaminase that is capable of mutating the cellular genome when acting aberrantly. Through mutagenic activity, APOBEC3A causes widespread base changes and DNA damage throughout the genome implicating the enzyme in genome instability. APOBEC3A is expressed in healthy hematopoietic cells, and his overexpressed in a subset of hematologic malignancies. The overall goal of the project is to determine how APOBEC3 mutagenesis impacts hematologic malignancies. Using models of APOBEC3A in hematopoietic progenitor cells, we will evaluate the hypothesis that mutagenesis by APOBEC3A contributes to malignant transformation and cancer progression. The objectives of this project are to determine the cellular factors that affect somatic mutagenesis by APOBEC3A deamination and to determine the impact of APOBEC3A on cellular transformation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1192622
Entities
People
- Abby M Green
Organizations
- Washington University in St. Louis