THE HYPERMUTABILITY CONFERRED BY THE MUS308 MUTATION OF DROSOPHILA ISNOT SPECIFIC FOR CROSS-LINKING AGENTS

The hypersensitivity of the mus308 mutant of D. melanogaster to cross- linking agents has been suggested to be the consequence of a possible defect of this mutant in DNA cross-link repair. Moreover, the mus308 m utation has been proposed as an animal model for the study of Fanconi' s anemia. In order to obtain more information about the function contr olled by this locus, we have measured the mutability of the mus308 mut ant to several mutagens with different modes of action using the sex-l inked recessive lethal test. We show that this mutation confers hyperm utability not only to the cross-linking agents tested, hexamethylphosp horamide and hexamethylmelamine, but to the point mutagen N-ethyl-N-ni trosourea as well, whereas the response to methyl methanesulfonate was normal. The results suggest that the mus308 locus is not defective in a repair pathway specific for cross-links but is rather involved in a step of a more general post-replication repair process responsible fo r the removal of non-excised adducts.