Molecular mechanisms of DNA interstrand cross-link repair in Saccharomyces cerevisiae

Project leader: Miroslav Chovanec
Project duration: 2009 - 2011

DNA interstrand cross-link (ICL) repair in eukaryotes, in contrast to prokaryotes, have proved more difficult to define, primarily as a result of the fact that several pathways compete for ICL repair intermediates. In this respect, budding yeast has proven a powerful tool for dissecting ICL repair in eukaryotes. Important roles for nucleotide excision repair, homologous recombination and post-replication/translesion synthesis pathways have all been identified. Our preliminary data indicates a role of Mgm101 in the ICL repair. Although mgm101 cells are not impaired in mismatch repair (MMR), they do show a defect analogous to MMR mutants during the ICL repair. Since the loss of MGM101 leads to increase in ICL sensitivity of pso2 cells, Mgm101 likely acts redundantly with Pso2, but epistatically with MMR, during the ICL repair. Our pilot data also suggests involvement of Mph1 in the Mgm101-MMR-dependent branch of the ICL repair. This project is undertaken to characterize this branch of the ICL repair in detail.