Our studies on DNA damage repair have spanned a diverse array of topics. In one set of studies, we explored the bacterial DNA damage responses that regulate the expression of various DNA repair mechanisms (PMID 37148591). 

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a. Can we identify novel DDR pathways, and dissect their mechanisms of regulation? Here, we discovered a conserved but uncharacterized transcription factor ccna_03845 (‘Cada2’) in Caulobacter crescentus. We showed that Cada2 regulates a methylation DNA damage-specific pathway, which showcases key features of an adaptive response. Our work suggests the divergence and co-evolution of the adaptive response transcription factors and their cognate sequence-specific DNA motifs across the bacterial kingdom (PMID 38466718).

b. Can we attest the universality of regulatory principles governing the conserved SOS response to DNA damage in bacteria? Our work on characterization of the SOS response in Caulobacter crescentus identified a distinct temporal hierarchy in the induction of SOS genes. We demonstrated that this hierarchy is independent of LexA properties. Instead, we revealed that intrinsic promoter strength drives the observed timing of gene induction. It is possible that promoter strength variation forms a fundamental regulatory layer for the development of temporal hierarchy in pathways across organisms (bioRxiv).​

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In another set of studies, we investigated the DNA damage response and repair mechanisms of yeast mitochondrial DNA (mtDNA). For this, we developed a system to induce mtDNA-specific damage. We engineered a mitochondrially-targeted bacterial DNA damage-inducing toxin, ‘mtDarT’, and tracked the effects of such damage on mitochondrial dynamics in real-time using quantitative live cell imaging approaches. Using this tool, we uncovered a function for the exonuclease activity of the mtDNA polymerase in mtDNA clearance upon damage (PMID 36074064; 39890960).