Our Primary Areas of Research are:
DNA repair, mutagenesis, and cellular responses to DNA damage
For more than three decades, this research has had a major impact on our understanding of how cells respond to damage to their DNA. It has made particularly important contributions to our knowledge of bacterial SOS responses to DNA damage and the crucial role that translesion DNA polymerases play in DNA damage tolerance and mutagenesis.
Function and control of translesion DNA polymerases in bacteria and eukaryotes
This research work focuses on a fundamental molecular mechanism by which virtually all organisms respond to environmental damage to their genetic material by carrying out translesion synthesis (TLS) over DNA lesions. The eukaryotic Rev1/3/7-dependent pathway of mutagenic TLS is critically important to human health, not only because it can help cells to survive by tolerating environmental DNA damage, including the repair of DNA crosslinks, but also because this molecular process is responsible for the vast majority of the mutagenesis that occurs as a result of damage to DNA. Mutations from environmental exposure contribute to cancer, other human diseases, and aging.
Molecular Genetics of Rhizobium Nodulation Plasmids
Our research work has had a major impact on our understanding of how Sinorhizobium meliloti invades nodules and establishes the chronic intracellular infection that underlies the symbiosis with its legume host. Our work has also identified common bacterial functions that are important for both symbiotic and pathogenic bacteria to interact with their respective eukaryotic hosts. In addition, it has also led to unanticipated fundamental discoveries, including the missing enzyme in vitamin B12 biosynthesis, and YbeY, a previously unrecognized, extremely highly conserved endoribonuclease that plays key roles in bacterial RNA metabolism and has human and plant homologs.