Current Research Interests:
One of the remaining mysteries in molecular genetics is the mechanism of recombination, especially in eukaryotic organisms. How does one small region of the very long DNA strands in homologous chromosomes line up, break and reseal without losing a single base pair, and produce two viable new recombinants? In E. coli recombination genes have been identified and these all affect various DNA transactions, often mutation and usually DNA repair. Recent progress with cloning of such yeast and human rec genes and isolation of their products is now giving first glimpses into various essential steps of recombination. I have been interested in this process for many years and am investigating recombination in fungi, mainly Aspergillus and also Neurospora, using two different approaches.
1) Mutants that affect DNA repair and therefore are hypersensitive to killing by UV, X-rays or carcinogens were isolated and tested for effects on recombination and also mutation. Some interesting, UV-sensitive, types affect both processes, while others, sensitive to chemical mutagens, only affect recombination. To identify effects of such mutants at the molecular level, recombination is being analysed in detail, within a sequenced gene region.
2) For analysis of interesting DNA repair and also cell cycle mutants which affect recombination, their genes are being cloned. Comparison to similar genes in other species can identify their primary function. For example, the Aspergillus gene uvsF, which acts in excision repair, codes for a well-conserved DNA replication factor (RFC1) and is required for DNA replication, but our mutant shows increased recombination. However uvsH, which is very similar and epistatic to uvst, recently has been sequenced by others, and is homologous to a yeast gene required for mutagenesis. Furthermore, a cloned cell cycle mutant, bimD, which also affects DNA repair, and uvsC, which is homologous to recA of E. coli, are both defective in recombination. Overall, we find interesting differences in the organization of repair in fungi compared to yeast