Functions and interactions of the Rad6 pathway in vertebrates

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The Rad6 epistasis group controls the bypass of DNA lesions during replication in yeast by either mutagenic translesion polymerases or by recombination based error free repair modes. Members of the Rad6 pathway are conserved in higher eukaryotes, but the exact degree of conservation of their function is unclear to date. Targeted mutagenesis and recombination play a major role in antibody diversification in the immune system, but it is unknown how repair pathway decision and recruitment of error-prone polymerases is regulated during these processes. We have found that the Rad6 pathway is involved in somatic hypermutation of immunoglobulin genes in the chicken B cell line DT40, suggesting that this pathway also controls the decision between mutagenesis and recombination during antibody diversification in vertebrates. In the present project, we wish to investigate in more detail the functions of the Rad6 pathway during general as well as targeted homologous recombination and mutagenesis in vertebrate cells. Also, we want to employ affinity purification to study the interactions of Rad6 pathway members with each other and with other pathways of DNA repair and cell cycle control.