Genetic controls of meiotic recombination and somatic DNA metabolism in Drosophila melanogaster.

Abstract

Recombination-defective meiotic mutants and mutagen-sensitive mutants of D. melanogaster have been examined for their effects on meiotic chromosome behavior, sensitivity to killing by mutagens, somatic chromosome integrity, and DNA repair processes. Several loci have been identified that specify functions that are necessary for both meiotic recombination and DNA repair processes, whereas mutants at other loci appear to be defective in only one pathway of DNA processing. Mutational analyses of prokaryotic systems have established that DNA replication, repair, and recombination are, in part, under common genic control (1-3). Although there are strong theoretical grounds for extending this conclusion to eukaryotes in general (4-7), direct experimental evidence for an interrelation of the various pathways of DNA metabolism in organisms that undergo meiosis comes primarily from studies of fungi (8, 9). Recombination-defective and repair-defective mutants have been reported in other eukaryotes (9, 10), although in most instances it is not known whether these mutants affect more than one pathway of DNA processing.In Drosophila melanogaster two classes of mutants with potential effects on DNA metabolism have been reported. First, substantial numbers of meiotic mutants are available, which were recognized because they produce genetically detectable abnormal meiotic chromosome behavior (for reviews see refs. 9, 11-14). Mutants at 12 loci are defective in processes essential for normal exchange (frequency and/or distribution along the chromosome) and are thus recombination-defective mutants. Watson (15,16) presented evidence that one of these recombination-defective mutants, c(3)G 17, is more susceptible than wild type to the induction of mutants and rearrangements during meiosis, and on this basis has suggested that the product of c(3)G + functions in both repair and recombination. Second, mutagen-sensitive mutants have been isolated on the basis of hypersensitivity to killing by methylmethanesulfonate (MMS) (17, 18,t). The characterization of meiotic mutants and mutagen-sensitive mutants (18, 19, ¶) by three separate groups using a variety of approaches has led to the realization that overlapping sets of mutants are being examined. In this preliminary communication we coordinate the results of the three groups and outline the conclusions concerning the relation between the genic controls of DNA repair processes and meiotic recombination in Drosophila. We focus here primarily on studies of several selected X-linked mutagen-sensitive and meiotic mutants. The detailed data on the arrays of mutants from which our conclusions have been derived will be published elsewhere.Known X-linked recombination-defective and/or mutagen-sensitive loci Recombination-defective mutants are known at 5 X chromosomal loci; mei-9, nmwi-218, me i-41, mei-352, and mei-251 (20, 21). In addition to decreasing the frequency and/or altering the distribution of exchanges along the chromosomes during female meiosis, these mutants all produce el...

Genetic control of chromosome breakage and rejoining in Drosophila melanogaster: spontaneous chromosome aberrations in X-linked mutants defective in DNA metabolism.

“…Independently of the correctness of the above suggestion, the present data fully confirm (10,16) that in D. melanogaster the same loci are used both in meiotic recombination and in maintaining the integrity of somatic chromosomes. Mutations at the mei-9 and mei-41 loci drastically reduce meiotic crossing-over and produce substantial increases in the frequencies of chromosome aberrations in neuroblast cells.…”

“…These mutants also differ in the distribution of breaks in the w y t The former designations of mus-109Dl and mus-109D2 were mus-107D1 and mus-107D2, respectively (10,11,15). During this study I realized that they produce the same pattern of chromosomal aberrations as mus-109Al (see Results).…”

“…DISCUSSION The present data clearly show that all mutant alleles at the mei-9, mei-41, mus-102, mus-105, and mus-109 loci produce substantial increases in the frequency of spontaneous chromosome aberrations. Baker et al (10,16) have inferred from the analysis of somatic spots in mutant flies that mutations at the mei-9 and mei-41 loci affect somatic chromosome stability.…”

“…However, in xeroderma pigmentosum cells, unlike mei-9 neuroblasts, no increase in the frequency of spontaneous chromosome aberrations is found (22). Another characteristic of mutants at the mei-9 locus that distinguishes them from excision-defective xeroderma pigmentosum mutants is their extreme sensitivity to methyl methanesulfonate and ionizing radiation (10,12,16). Furthermore mei-9 mutants show a drastic reduction in meiotic recombination (6), whereas individuals with xeroderma pigmentosum are probably not deficient in this function since they exhibit normal numbers of chiasmata in primary spermatocytes (23).…”

REC, a new member of the MCM-related protein family, is required for meiotic recombination in Drosophila.

“…Spontaneous double-strand breaks in somatic cells are repaired by either recombinational repair or non-homologous end-joining. Mutations defective in meiotic recombination frequently show mitotic defects, such as mutagen sensitivity (Baker et al, 1976). Conversely, mutants isolated by their sensitivity to mutagens frequently show meiotic defects.…”