Mutational specificity of ethyl methanesulfonate in excision-repair-proficient and -deficient strains of Drosophila melanogaster

Pastink, Albert; Heemskerk, E.; Nivard, Madeleine J.M.; Vliet, C. J. Van; Vogel, E.

doi:10.1007/bf00272158

Cited by 72 publications

(29 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequence analysis of the A17-11 DmRAD54 allele and comparison with the sequence of the wild-type allele of the cn bw strain revealed only a G-to-A transition at the splice acceptor site of the second intron (data not shown). This type of alteration is consistent with the fact that EMS induces mainly GC-to-AT transitions (43). The presence of a splice mutation in the A17-11 mutant might lead to the formation of unstable DmRAD54 mRNA, explaining why no DmRAD54 transcripts could be detected by blot hybridization.…”

Section: Resultssupporting

confidence: 83%

The Drosophila melanogaster RAD54 Homolog, DmRAD54, Is Involved in the Repair of Radiation Damage and Recombination

Kooistra

Vreeken

Zonneveld

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRAD54-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X-ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution.Double-strand breaks (DSBs) in DNA are induced by ionizing radiation and by various chemical compounds, such as free radicals and methyl methanesulfonate (MMS). In addition, DSBs arise as intermediates during V(D)J rearrangement in differentiating lymphocytes, transposition events, and meiotic recombination in germ cells. Unrepaired DSBs often lead to cell death or contribute to the formation of chromosomal aberrations such as deletions and translocations. In eukaryotes, DSBs can be repaired via two main pathways: (i) recombinational repair, which is dependent on the presence of an intact duplicate DNA sequence, and (ii) end-to-end rejoining, which is based on rejoining of the two DNA ends (46). The available evidence suggests that both mechanisms are conserved in eukaryotes from yeasts to humans. However, the relative contributions of both mechanisms in repair of DSBs differ considerably between lower and higher eukaryotes. Repair of DSBs in mammals has been investigated with radiation-sensitive rodent cell lines. Several of these cell lines have defects in repairing radiation-induced DSBs and are also strongly impaired in V(D)J rearrangement. Further studies have revealed that these mutants have defects in the end-to-end rejoining pathway (reviewed in references 26, 47, and 63). Repair of DSBs at defined sites in the genome of mammalian cells also occurs more frequently by end-to-end rejoining than by homologous recombination (21, 33). The same observations have been made in experiments studying the fate of linear plasmid molecules in mammalian cells and Xenopus laevis oocytes (27,29,31). Therefore, DSBs in higher eukaryotes appear to be repaired primarily by end-to-end rejoining mechanisms.In lower eukaryotes, however, repair of DSBs occurs almost exclusively by...

show abstract

Section: Resultssupporting

confidence: 83%

The Drosophila melanogaster RAD54 Homolog, DmRAD54, Is Involved in the Repair of Radiation Damage and Recombination

Kooistra

Vreeken

Zonneveld

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…The ability of EMS to induce excision repairable lesions has already been demonstrated in a wide range of eukaryotic organisms, including Drosophila, rodents, and humans (Pastink et al, 1991;Selden et al, 1993;Bentley et al, 1994;Jansen et al, 1996). Most of the lesions induced by EMS are 7-alkylguanines, although 3-alkyladenine, 7-alkyladenine, and O 6 -alkylguanine are also produced.…”

Section: Discussionmentioning

confidence: 91%

Low level of DNA repair in human chromosome 1 heterochromatin

Surrallés

Darroudi

Natarajan

1997

Genes Chromosom. Cancer

View full text Add to dashboard Cite

“…In general, DNA damage induced by environmental mutagens is repaired predominantly by nucleotide excision repair [Hartwig and Schwerdtle, 2002] and the ability of EMS to induce excision-repairable lesions has been demonstrated in a wide range of eukaryotic organisms, including Drosophila, rodents, and humans [Pastink et al, 1991;Selden et al, 1993;Bentley et al, 1994]. On the other hand, most of the damage induced by PDC results from the generation of free radicals and activated oxygen species [Gate et al, 1999;Rizki et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

Genotoxicity modulation by cadmium treatment: Studies in the Drosophila wing spot test

Rizki

Kossatz

Creus

et al. 2004

Environ and Mol Mutagen

View full text Add to dashboard Cite

The genotoxic activity of cadmium chloride (CC) has been evaluated in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. In addition, its possible modulating effect on the genotoxicity of two known mutagenic agents, potassium dichromate (PDC) and ethyl methanesulfonate (EMS), was investigated. Three different types of combined treatments of CC with the two genotoxins were performed: pretreatment, cotreatment, and posttreatment. The SMART assay is based on the principle that loss of heterozygosity for the recessive markers, multiple wing hairs (mwh) and flare-3 (flr(3)), leads to the formation of mutant clones in the imaginal disks of larvae, which are expressed as mutant spots on the wings of adult flies. Thus, after adult emergence, the wings of the adult flies were scored for the presence of single and/or twin spots. Our results show that CC alone was not effective in increasing the frequency of any of the three categories of spots (small, large, and twin). In the cotreatment experiments, CC increased the genotoxicity of PDC but it decreased the genotoxicity of EMS. No effects of CC were observed in the pretreatment or posttreatment experiments; however, only low concentrations of CC, PDC, and EMS were tested in the pretreatment assays due to the high toxicity of the treatment. Although our results with PDC are consistent with the hypothesis that cadmium can interfere with repair mechanisms, the EMS data suggest that other modulating mechanisms are also involved in the genotoxicity of this metal.

show abstract

Mutational specificity of ethyl methanesulfonate in excision-repair-proficient and -deficient strains of Drosophila melanogaster

Cited by 72 publications

References 38 publications

The Drosophila melanogaster RAD54 Homolog, DmRAD54, Is Involved in the Repair of Radiation Damage and Recombination

The Drosophila melanogaster RAD54 Homolog, DmRAD54, Is Involved in the Repair of Radiation Damage and Recombination

Low level of DNA repair in human chromosome 1 heterochromatin

Genotoxicity modulation by cadmium treatment: Studies in the Drosophila wing spot test

Contact Info

Product

Resources

About