Elucidating the function of YedK in response to DNA damage

Apurinic/Apyrimidinic (AP) sites are one of the most prevalent forms of DNA damage. These lesions arise spontaneously or during base excision repair of modified DNA bases and are potentially mutagenic in both mammalian and bacterial cells. 5-hydroxymethylcytosine binding, ES cell specific (HMCES), a protein found in eukaryotic cells, has been shown to form a stable DNA-protein crosslink with AP sites in single stranded DNA and to reduce the number of AP sites occurring either spontaneously or after alkylative DNA damage, resulting in increased genome stability. YedK, the Escherichia coli ortholog of HMCES exhibits some of the same biochemical properties as HMCES. However, less is known about the in vivo role of YedK. Here, I characterized the behavior of yedK mutants treated with methyl methanesulfonate and tertbutyl hydroperoxide, two agents that are predicted to generate AP sites as repair intermediates. I found that the absence of yedK had no impact on the survival of cells following exposure to methyl methanesulfonate, which generates alkylative DNA damage. Cells lacking yedK were more resistant to oxidative DNA damage induced by tert-butyl hydroperoxide compared to their wild-type parent. However, this increased resistance was dependent on functional translesion synthesis and base excision repair. I discuss these results in relation to what is known about HMCES function in mammalian cells.