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mus308 mutants of Drosophila exhibit hypersensitivity to DNA cross-linking agents and are defective in a deoxyribonuclease.

Abstract
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.
AuthorsJ B Boyd, K Sakaguchi, P V Harris
JournalGenetics (Genetics) Vol. 125 Issue 4 Pg. 813-9 (Aug 1990) ISSN: 0016-6731 [Print] United States
PMID2397884 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cross-Linking Reagents
  • Mutagens
  • Mechlorethamine
  • DNA
  • Deoxyribonucleases
  • Ficusin
Topics
  • Animals
  • Cross-Linking Reagents
  • DNA (drug effects)
  • DNA Repair
  • Deoxyribonucleases (genetics, metabolism)
  • Drosophila (enzymology, genetics)
  • Ficusin (pharmacology)
  • Genes
  • Mechlorethamine (pharmacology)
  • Mutagens
  • Mutation

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