The APOBEC3 cytidine deaminase family has been made famous for their ability to restrict viral replication as important innate immune factors. These enzymes have the ability to deaminate cytisine in ssDNA to uracil, which in turn is read as thymine during dna replication. These events will lead to C->T mutations throughout a genome. APOBEC3G will hypermutate ssDNA intermediate of the HIV genome during replication, as well as APOBEC3B editing adenoviruses during their nuclear replication cycle.
In recent years, APOBEC3A (A3A) and APOBEC3B have both been implicated in tumorigenesis. As A3A is known to restrict viruses as well as reduce cellular inflammation by clearing cytoplasmic DNA, it is know also known that it can travel back into the nucleus and cause C->T mutations in genomic DNA. Cancer genomes are riddled with C->T mutations, which have been linked the A3A and A3B activity.
Our group has previously shown that the protein Tribble3 is capable of protecting the genome from APOBEC editing. As you knock down Tribble3, the proto-oncogene MYC becomes hypermutated by APOBEC3A.
Our team is now interested in finding other factors that may help protect the genome from consequential editing by the A3 enzymes.
