Mutagenesis in Meiosis

This project aims to investigate the mechanisms underlying the formation of single-stranded DNA (ssDNA) during meiosis, with a particular focus on the DNA repair mechanisms of SPO11-induced double-strand breaks (DSBs). One of the main goals is to explore how these DNA repair processes can contribute to genome instability by promoting accumulation of long tracts of mutagenic ssDNA. By utilizing the human APOBEC3A (A3A) enzyme, which targets and induces mutations specifically in ssDNA, the project seeks to map the frequency and distribution of such mutagenic events in the meiotic yeast genome by utilizing whole-genome sequencing techniques. By investigating the relationship between the observed meiotic recombination events and patterning of A3A-induced mutation clusters within long mutagenic ssDNA, this project aims to parse the who, the how, and when of the abnormal meiotic DSBs repair. Understanding the circumstances that lead to the formation of mutagenic ssDNA is critical for elucidating how meiotic processes can result in mutagenesis and genetic variation, with potential implications for both evolution and disease.