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Genetic basis of the effect of alkylating agents on gametogenesis in drosophila melanogaster Schewe, Michael Joseph

Abstract

The antibiotic, Mitomycin-C (MC), increases recombination in Drosophila females, yet has no effect on crossing over in males. This sexual difference in recombinagenic response to MC cannot be attributed to a sex difference in permeability to MC, since MC is mutagenic in both sexes. MC increases the frequency of exchange events involving X and Y chromosomes as well as those involving the two arms of the Y in both sexes. On the basis of brood analysis it was found that those cells which are most sensitive to the recombinagenic and X-Y and Y-Y exchange effects of MC were in a premeiotic stage of gametogenesis at the time of treatment. It is proposed that the apparent inability of MC to induce crossovers in males is related to the normal absence of spontaneous meiotic crossing over in males. MC can act as a monofunctional or as a bifunctional alkylating agent which primarily reacts with guanine residues of DNA. Bifunctional alkylation results in the crosslinking of the two strands in the DNA double helix. It is postulated that prior to meiosis, alkylated guanine residues are excised from the DNA molecule through the action of natural repair mechanisms. Depending on whether mono or bifunctional alkylation has taken place, either single strand nicks or double strand cuts will be induced in the DNA. Double strand cuts may be repaired as a mutation or as a non-reciprocal exchange event whereas single strand nicks might act as the natural pre-condition for genuine meiotic crossovers and could thus form crossovers when the necessary "crossover substances" are present. This model predicts that an alkylating agent such as ethyl methanesulfonate (which alkylates guanine monofunction-ally, and therefore would give rise to single strand nicks following excision), should be recombinagenic in females, but not in males but should not effect the frequency of X-Y and Y-Y exchange events in either sex. This prediction was indeed demonstrated thus supporting the model.

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