Horizontal gene transfer of two cytoskeletal elements from a eukaryote to a cyanobacterium

cytotoxicity of MNNG. Shown in Figure 1B is a schematic incorporating the DCD1related findings reported here and those from a previous report [2]. The MMR-dependent response to Sn1-type methylating agents most likely involves additional proteins besides those normally associated with MMR-dependent spellchecking (for a review, see [1]). Our study has uncovered one such protein, Dcd1, which modulates dCTP:dTTP pool levels and therefore influences sensitivity to agents that induce formation of O6metG. Several studies with cultured rodent cells suggested that Dctd deficiency increased the dCTP:dTTP pool ratio [7–9]. However, we are not aware of any isogenic pairs of proficient/deficient cell lines to test rigorously the role of Dctd in the response to methylation damage. Of interest, however, Meuth [7] showed that elevated dTTP pools increased sensitivity to MNNG in Chinese hamster ovary cells and speculated that misincorporation of thymine opposite O6metG was the basis for the observed toxicity. Finally, our findings may also have relevance to cancer chemotherapy. For example, reduced DCTD levels in a tumor might compromise the clinical response to the Sn1-type methylation agent temozolomide or the purine analog 6-mercatopurine, used in the treatment of glioblastoma multiforme [10] and certain hematological malignancies [11], respectively.