Anton Gartner Lab

On average, only one mutation occurs in a C. elegans generation, and only ~20 germline mutations occur in a human generation. The question of how such high fidelity is achieved is still the subject of many research efforts, and redundant DNA repair pathways appear to be a key mechanism. For example, branched DNA structures that arise as intermediates in DNA metabolism can be processed by the Mus81, Slx1, and Gen1 nucleases. Nevertheless, some branched molecules persist into mitosis and result in DNA bridges in a large fraction of dividing cells. The processing of those DNA bridges is important to prevent aneuploidy and disease. We recently discovered that the conserved LEM-3/Ankle1 nuclease resolves these bridges using C. elegans. We will elucidate the mechanisms by which LEM-3/Ankle1 acts and study this process in more detail and now also use mammalian cells. The acquisition of mutations is an intrinsic feature of all cells despite the vast majority of primary DNA lesions being removed by repair pathways. Although DNA damage and repair pathways have been extensively studied, there is limited understanding of mutational processes operating in eukaryotic cells in vivo. The advent of next-generation sequencing provides the power to detect and characterize large sets of mutations and to determine mutational patterns, providing a new opportunity to understand mutagenesis and various DNA repair processes that mend damaged DNA as well as the interplay between them. Mutational patterns associated with known mutagens, DNA repair deficiencies, or a combination thereof can be compared to mutational signatures derived from cancer genomes, and provide the opportunity to explain the mutagenic processes that drive cancer progression. Paradoxically, the majority of chemotherapeutic an