mus308 mutants of Drosophila exhibit hypersensitivity to DNA cross-linking agents and are defective in a deoxyribonuclease.
Mutagen-sensitive strains that identify 16 different Drosophila genes have been screened for alterations in DNA metabolic enzymes. A characteristic defect in an acid-active deoxyribonuclease was observed in strains carrying the six available mutant alleles of the mus308 gene. Since that enzyme is detected at normal levels in a mutant strain that is deficient in the previously identified enzymes DNase 1 and DNase 2, it represents a new Drosophila nuclease that is designated Nuclease 3. The mus308 mutants were originally distinguished from all other mutagen-sensitive mutants of Drosophila because they exhibit hypersensitivity to the DNA cross-linking agent nitrogen mustard without expressing a concurrent sensitivity to the monofunctional agent methyl methanesulfonate. Further observations of hypersensitivity to the mutagens trimethylpsoralen, diepoxybutane and cis-platinum now establish a more general sensitivity of these mutants to agents capable of generating DNA cross-links. In spite of the hypersensitivity of the mus308 mutants to DNA cross-linking agents, the initial incision step of DNA cross-link repair is normal in mus308 cells as assayed by the alkaline elution procedure. The Drosophila mus308 mutants show promise of providing a useful model for analogous defects in other organisms including man.
Department of Genetics, University of California, Davis 95616.
J B
JB
Boyd
K
K
Sakaguchi
P V
PV
Harris
D000818:Animals; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects; D004260:DNA Repair; D003851:Deoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology / Q000235:genetics*; D005363:Ficusin / Q000494:pharmacology; D005796:Genes; D008466:Mechlorethamine / Q000494:pharmacology*; D009153:Mutagens; D009154:Mutation
D003432:Cross-Linking Reagents; D009153:Mutagens; D008466:Mechlorethamine; D004247:DNA; D003851:Deoxyribonucleases; D005363:Ficusin