The mus308 locus of Drosophila melanogaster is implicated in the bypass of ENU-induced O-alkylpyrimidine adducts

Mol Gen Genet. 2000 Feb;263(1):144-51. doi: 10.1007/s004380050041.

Abstract

The mus308 locus of D. melanogaster was originally characterized by virtue of a mutant phenotype that resulted in specific hypersensitivity to cross-linking agents. However, the gene product has also been implicated in the repair of lesions other than cross-links. The gene was recently sequenced, and it encodes a protein with motifs characteristic of both DNA polymerases and helicases. We present mutability studies, using the recessive lethal (RL) test, which show that N-ethyl-N-nitrosourea (ENU) induces hypermutability in mus308-deficient conditions, although only in early broods. Further studies elucidated the role of MUS308 in repair processes by characterizing the spectrum of molecular mutations induced by in vivo ENU in postmeiotic germ cells, in mus308 conditions. These revealed that, in comparison to repair-proficient conditions, there is an increase in the frequency of GC --> AT and AT --> GC transitions, and AT --> TA transversions. Moreover, frameshift mutations, which have not previously been reported to form part of the ENU spectrum, were also found. These results indicate that MUS308 is needed to process ENU-induced lesions, and support the hypothesis that the mus308 gene plays a role in post-replication bypass of O-alkylpyrimidines, probably mediated by recombination, which serves to increase the time available for error-free repair of these persistent and highly mutagenic lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA / drug effects
  • DNA / genetics
  • DNA / metabolism
  • DNA Adducts / metabolism*
  • DNA Primers / genetics
  • DNA Repair
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Ethylnitrosourea / toxicity
  • Female
  • Genes, Insect*
  • Genes, Lethal
  • Genes, Recessive
  • Male
  • Mutation

Substances

  • DNA Adducts
  • DNA Primers
  • DNA
  • Ethylnitrosourea