The role and the contribution of Escherichia coli and Schizosaccharomyces pombe alkyltransferase homologues (ATL| in the repair of DNA alkylation damage in yeast Saccharomyces cerevisiae

Project leader: Karol Kleibl
Project duration: 2008 - 2010

In silico analysis revealed a group of genes, called the alkyltransferase-like (ATL) due to their similarity to the of O6-methylguanine DNA-methyltransferase (MGMT), which removes the alkylating damage from O6 atom of guanine. In these homologues the cysteine residue in the putative active site is repalced by tryptophane, their function is unknown but the sequence similarity to MGMT suggests a role in the repair of alkylated damage. E. coli contains two different MGMT genes besides the ATL protein, which was purified and shown to inhibit the transfer of methyl group to human MGMT and binds to DNA, containing O6-meG. S. cerevisiae and most of eukaryotes contain the MGMT but no ATL gene, whilst S. pombe codes only for ATL. To establish its role in vivo, using the atl1 mutants it was shown that they are more susceptible to the toxic effects of alkylating agents than a wild-type and in vitro analysis confirmed the E. coli results. Project will study the role of ATL proteins in the model of S. cerevisiae.