Mutational Signatures

Patterns of single base substitution (SBS) mutations have been identified across cancer genomes and provide insight into mutagenic factors contributing to human cancers. Two SBS mutational patterns are attributed to the activity of APOBEC3 enzymes, which deaminate cytidine bases in single-stranded DNA. In collaboration with the lab of Dr. David Szuts at the Hungarian Academy of Sciences, we have generated a system for modeling APOBEC3A mutagenesis using avian cells and have experimentally defined the mutational signature generated by APOBEC3A. We are use this system to examine the mechanisms by which APOBEC3 mutational patterns occur, DNA repair factors that impact APOBEC3 mutagenesis, and cellular contexts that alter the APOBEC3 mutational signature. In addition, we are investigating mutational signatures incurred by other endogenous and exogenous mutagens.

The experimentally-defined mutational spectrum of APOBEC3A activity in avian cells. We found the mutational signature caused by APOBEC3A in avian cells closely matches SBS2 and SBS13, mutational patterns found in cancer that have been attributed to deaminase activity.

The experimentally-defined mutational spectrum of APOBEC3A activity in avian cells. We found the mutational signature caused by APOBEC3A in avian cells closely matches SBS2 and SBS13, mutational patterns found in cancer that have been attributed to deaminase activity.

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APOBEC3 Deaminases