Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage
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Abstract:
Drosophila melanogaster males from a Basc stock were mutagenized with either X-rays, ethyl methanesulfonate (EMS), or nitrogen mustard (HN2). Groups of identically treated males were crossed to different types of female. Sex-linked recessive lethals were scored as a genetic end point. The females used were homozygous for X-chromosomal mutations (mus(1)101D1, mus(1)104D1, mei-9 or mei-41D5) which lead to defective DNA repair and which increase the mutagen sensitivity of larvae. Females from a white stock with normal DNA repair capacities served as controls. The premutational lesions induced in mature sperm are only processed after insemination by the maternal enzyme systems present in the oocytes. Differences in the efficiency of the processing of lesions can lead to maternal effects on the frequency of mutations recovered from mutagenized sperm. It was found that, with the exception of mus(1)104D1, all mutants analysed significantly modify the mutation fixation of one or more types of premutational lesions. The most drastic effect is found with the mus(1)101D1 stock in which HN2-induced DNA cross-links do not lead to sex-linked recessive lethals. It is assumed that mus(1)101D1 is defective in an early step of DNA cross-link repair. Our first set of data clearly demonstrates that the study of maternal effects in Drosophila is an efficient tool to analyse the in vivo function of repair mutations on chemically induced mutagenesis.
Insights
Maternal DNA repair genes in Drosophila significantly impact mutation outcomes. Specific mutations, like mus(1)101D1, reveal defects in repairing DNA damage, highlighting the importance of maternal effects in mutagenesis studies.
Area of Science:
- Genetics
- Molecular Biology
- Toxicology
Background:
- DNA repair mechanisms are crucial for maintaining genomic integrity.
- Maternal genetic factors can influence offspring mutation rates.
- Drosophila melanogaster is a model organism for studying mutagenesis and DNA repair.
Purpose of the Study:
- To investigate the role of maternal DNA repair pathways in processing mutagen-induced DNA lesions.
- To analyze how specific mutations affecting DNA repair influence the fixation of premutational lesions in Drosophila.
- To assess the utility of maternal effects in Drosophila for studying in vivo repair gene function.
Main Methods:
- Mutagenesis of Drosophila melanogaster males using X-rays, ethyl methanesulfonate (EMS), and nitrogen mustard (HN2).
- Crossing mutagenized males to females homozygous for DNA repair mutations (mus(1)101D1, mus(1)104D1, mei-9, mei-41D5) or control females.
- Scoring sex-linked recessive lethals as a measure of mutation frequency.
Main Results:
- Most maternal DNA repair mutants significantly altered the frequency of recovered mutations.
- The mus(1)101D1 mutant showed a complete absence of sex-linked recessive lethals for nitrogen mustard-induced DNA cross-links.
- This suggests a defect in an early DNA cross-link repair step in mus(1)101D1.
Conclusions:
- Maternal effects in Drosophila provide an effective method for dissecting in vivo DNA repair gene functions.
- Specific maternal repair mutations can differentially affect the processing of various premutational lesions.
- The mus(1)101D1 mutation highlights a critical role for early-acting repair pathways in preventing mutations from nitrogen mustard.