DOE Human Genome Program Contractor-Grantee Workshop VIII
February 27-March 2, 2000  Santa Fe, NM

101. The Molecular Genetics of DNA Repair in Drosophila

K.C. Burtis, R.S. Hawley, C. Boulton, K. Hollis, A. Laurencon, and D. Milliken

Section of Molecular and Cellular Biology, University of California at Davis, Davis, CA 95616

shawley@netcom.com

Screening for new repair-deficient mutants:

To date we have screened approximately 12,100 of 12,500 available lines of EMS induced mutations on the 2^nd and 3^rd chromosomes from the Zuker collection. Thus far we have both identified and confirmed by retest approximately 60 lines that display significant sensitivity to one or more mutagens. We are currently assigning the newly-isolated mutants to complementation groups as well as testing them for allelism with existing 2^nd and 3^rd chromosome mus mutations.

Characterization of existing mutagen-sensitive mutations:

We are in the process of carefully mapping the existing collection of mutagen-sensitive mutations. In several cases we have refined the map positions down to small genetic intervals and are testing P element insertions in the region for their ability to complement these mutations. In most cases however we are still in the process of positioning the mutant to within a numbered unit on the polytene chromosome. We have also continued our molecular and genetic characterization of two Drosophila ATM homologs. For one of these genes, mei-41, we have completed a synthetic lethal screen and begun a genetic fine structure analysis of existing mutant alleles.

Microarrays:

Glass slide microarrays have been produced that include over 10,000 Drosophila cDNAs. The cDNAs are derived from the Berkeley Drosophila Genome Project Unigene set, as well as from a set of testes-specific cDNAs generated by Dr. Brian Oliver at the NIDDK. We will report the results of our initial array experiments examining changes in gene expression resulting from exposure of Drosophila to various doses of ionizing radiation.

Genomics:

A comprehensive summary of Drosophila homologs of approximately 90 known DNA repair genes will be presented. This summary is based on analysis of the complete sequence of the Drosophila genome developed by Celera Genomics in collaboration with the Berkeley Drosophila Genome Project. Also integrated into this analysis is our current data regarding the association of these sequences with extant Drosophila mutagen-sensitive mutations.