Induced chromosome loss following treatment of postmeiotic cells of the Drosophila melanogaster male with MMS and DMN and matings with repair-proficient females and the repair-deficient females mei-9a and st mus302

Drosophila melanogaster ring-X males carrying a double marked Y chromosome, BsYy+, were treated with MMS or DMN and mated with repair-proficient females or the repair-deficient females mei-9a and st. mus302. Frequencies of induced complete loss (principally the ring-X) and partial losses of the Y chromosome (loss of Bs or Y+) decreased in the sequence st must302 greater than mei-9a greater than repair-proficient females agreeing with the sequence obtained previously with procarbazine and DEN. With MMS and DMN, some 30-40% or more or partial Y chromosome losses are mosaics from mei-9a and only 0.4% from st mus302 females and a delay in mei-9a females. Similar findings with procarbazine and DEN are indicated. That the higher sensitivity of st mus302 relative to mei-9a results from impairments in both postreplication and excision repair in the former remains to be determined.     

Mutations at the mei-41, mus(1)101, mus(1)103, mus(2)205 and mus(3)310 loci of Drosophila exhibit differential UDS responses with different DNA-damaging agents

5 mutagen-sensitive mutants of Drosophila melanogaster, reported to perform normal or only slightly reduced excision repair of UV damage, were examined by an unscheduled DNA synthesis (UDS) assay. This assay measures the ability of cultured primary cells, derived from each mutant, to perform the resynthesis step in the excision repair pathway, following damage to cellular DNA by direct-acting alkylating agents, UV or X-irradiation. 2 mutants, classified as completely or partially proficient for both excision and postreplication repair of UV damage, mus(1)103 and mus(2)205, were found to give positive UDS responses only for UV damage. These mutants exhibit no measurable UDS activity following DNA damage by several different alkylating agents and X-rays. 3 mutants, classified as having no defect in excision repair, but measurable defects in postreplication repair of UV damage, mei-41, mus(1)101, and mus(3)310 exhibit 3 different response patterns when tested with the battery of agents in the UDS assay. The mutant mei-41 exhibits a highly positive UDS response following damage by all agents, consistent with its prior classification as excision-repair-proficient, but postreplication-repair-deficient for UV damage. The mutant mus(1)101, however, exhibits a strong positive UDS response following only UV damage and appears to be blocked in the excision repair of damage produced by both alkylating agents and X-irradiation. Finally, mus(3)310 exhibits no UDS response to alkylation, X-ray or UV damage. This is not consistent with its previous classification. Results obtained with the quantitative in vitro UDS assay are entirely consistent with the results from two separate in vivo measures of excision repair deficiency following DNA damage, larval hypersensitivity to killing and hypermutability in the sex-linked recessive lethal test.     

Hypersensitivity of Drosophila mei-41 mutants to hydroxyurea is associated with reduced mitotic chromosome stability

6 mutant alleles of the mei-41 locus in Drosophila melanogaster are shown to cause hypersensitivity to hydroxyurea in larvae. The strength of that sensitivity is directly correlated with the influence of the mutant alleles on meiosis in that: alleles exhibiting a strong meiotic effect (mei-41D2, mei-41D5, mei-41D7) are highly sensitive; alleles with negligible meiotic effects (mei-41(104)D1, mei-41(104)D2) are moderately sensitive and an allele which expresses meiotic effects only under restricted conditions (mei-41D9) has an intermediate sensitivity. This sensitivity is not a general feature of strong postreplication repair-deficient mutants, because mutants with that phenotype from other loci do not exhibit sensitivity (mus(2)205A1, mus(3)302D1, mus(3)310D1). The observed lethality is not due to hypersensitivity of DNA synthesis in mei-41 larvae to hydroxyurea as assayed by tritiated thymidine incorporation. Lethality is, however, potentially attributable to an abnormal enhancement of chromosomal aberrations by hydroxyurea in mutant mei-41 larvae. Both in vivo and in vitro exposure of neuroblast cells to hydroxyurea results in an increase in 3 types of aberrations which is several fold higher in mei-41 tissue. Since hydroxyurea disrupts DNA synthesis, these results further implicate the mei-41 locus in DNA metabolism and provide an additional tool for an elucidation of its function. The possible existence of additional genes of this nature is suggested by a more modest sensitivity to hydroxyurea which has been detected in two stocks carrying mutagen-sensitive alleles of alternate genes.     

High frequency of spontaneous Minute mutations detected in the F1 progeny of interstrain matings between a recombination-defective mei-9L1 and the y w m f/sc8(y+) Y BS; dp strain of Drosophila melanogaster

The yield of spontaneous Minute mutations was recorded in the F1 progeny of interstrain (reciprocal) and intrastrain matings between a recombination- and excision repair-defective mei-9L1 (mei-9) strain and the y w m f/sc8(y+) Y BS; dp (ywmf-2) strain of Drosophila melanogaster. As a comparison, interstrain matings between a postreplication repair-defective st mus(3)302D1 (mus(3)) strain and the ywmf-2 strain were also studied for Minute mutations. The results show that: (1) a strikingly high frequency of Minute mutations is observed in the progeny of mei-9 female X ywmf-2 male crosses, but not in that of ywmf-2 females X mei-9 males; (2) no such difference exists in the progeny of intrastrain matings; and (3) there exists no marked inequality of Minute frequencies in the progeny of reciprocal crosses of mus(3) and ywmf-2 strains.     

Studies on mutagen-sensitive strains of Drosophila melanogaster. IV. Modification of genetic damage induced by X-irradiation of spermatozoa and spermatids in N2 or O2 by mei-9a, mei-41D5 and mus(1)101D1

The influence of defects in DNA repair processes on X-ray-induced genetic damage in post-meiotic male germ cell stages of Drosophila melanogaster was studied using the 'maternal effects approach'. Basc males were irradiated in N2, air or O2 either as 48-h-old pupae (to sample spermatids) or as 3-4-day-old adults (to sample mature spermatozoa) and mated to females of 3 repair-deficient strains (mei-9a: excision-repair-deficient; mei-41D5: post-replication-repair-deficient; mus(1)101D1: post-replication-repair-deficient and impaired in DNA synthesis). Simultaneous controls involving mating of males to repair-proficient females (mei+) were run. The frequencies of sex-linked recessive lethals and of autosomal translocations were determined following standard genetic procedures. The responses elicited in the different crosses with repair-deficient females were compared with those in mei+ crosses. The main findings are the following: with mei-9 females, the frequencies of recessive lethals are higher after irradiation of spermatids in N2, but not after irradiation in air of O2 (relative to those in the mei+ crosses); this result is different from that obtained in earlier work with spermatozoa, in which cell stage, higher yields of recessive lethals were obtained after irradiation of males in either N2 or air; in the mei-9 crosses, there are no significant differences in response (relative to mei+) after irradiation of either spermatozoa or spermatids in O2; the translocation frequencies in the mei-9 crosses are similar to those in the mei+ crosses, irrespective of the treated germ cell stage or the irradiation atmosphere; irradiation of either spermatozoa or spermatids in N2, air or O2 does not result in any differential recovery of recessive lethals in the mei-41 relative to mei+ crosses; irradiation of spermatids in N2 and of spermatozoa in air leads to a higher recovery of translocations in the mei-41 crosses; and after irradiation of spermatids or spermatozoa in any of the gaseous atmospheres, the frequencies of recessive lethals and of translocations are lower in the mus-101 crosses. The differences in responses (between cell stages, in different gaseous atmospheres and with different repair-deficient females) are explained on the basis of both qualitative and quantitative differences in the composition of the initial lesions and the extent to which their repair may be affected by the defects present in the different repair-deficient females. Several discrepancies between expectations based on biochemical results and the genetic results are pointed out.(ABSTRACT TRUNCATED AT 400 WORDS)     

The relationship between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems. IV. The effects of the excision-defective mei-9L1 and mus(2)201D1 mutants on alkylation-induced genetic damage in Drosophila

Repair-defective mutants of Drosophila melanogaster which identify two major DNA excision repair loci have been examined for their effects on alkylation-induced mutagenesis using the sex-linked recessive lethal assay as a measure of genotoxic endpoint. The alkylating agents (AAs) chosen for comparative analysis were selected on the basis of their reaction kinetics with DNA and included MMS, EMS, MNU, DMN, ENU, DEN and ENNG. Repair-proficient males were treated with the AAs and mated with either excision-defective mei-9L1 or mus(2)201D1 females or appropriate excision-proficient control females. The results of the present work suggest that a qualitative and quantitative relationship exists between the nature and the extent of chemical modification of DNA and the induction of of genetic alterations. The presence of either excision-defective mutant can enhance the frequency of mutation (hypermutability) and this hypermutability can be correlated with the Swain-Scott constant S of specific AAs such that as the SN1 character of the DNA alkylation reaction increases, the difference in response between repair-deficient and repair-proficient females decreases. The order of hypermutability of AAs with mei-9L1 relative to mei-9+ is MMS greater than MNU greater than DMN = EMS greater than iPMS = ENU = DEN = ENNG. When the percentage of lethal mutations induced in mei-9L1 females are plotted against those determined for control females, straight lines of different slopes are obtained. These mei-9L1/mei-9+ indices are: MMS = 7.6, MNU = 5.4, DMN = 2.4, EMS = 2.4 and iPMS = ENU = DEN = ENNG = 1. An identical order of hypermutability with similar indices is obtained for the mus(2)201 mutants: MMS(7.3) greater than MNU (5.4) greater than EMS(2.0) greater than ENU(1.1). Thus, absence of excision repair function has a significant effect on mutation production by AAs efficient in alkylating N-atoms in DNA but no measurable influence on mutation production by AAs most efficient in alkylating O-atoms in DNA. The possible nature of these DNA adducts has been discussed in relation to repair of alkylated DNA. In another series of experiments, the effect on alkylation mutagenesis of mei-9L1 was studied in males, by comparing mutation induction in mei-9L1 males vs. activity in Berlin K (control). Although these experiments suggested the existence of DNA repair in postmeiotic cells during spermatogenesis, no quantitative comparisons could be made.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage.

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.     

P transposition in Drosophila provides a new tool for analyzing postreplication repair and double-strand break repair.

A genetic screen has been developed in Drosophila for identifying host-repair genes responsible for processing DNA lesions formed during mobilization of P transposable elements. Application of that approach to repair deficient mutants has revealed that the mei-41 and mus302 genes are necessary for recovery of P-bearing chromosomes undergoing transposition. Both of these genes are required for normal postreplication repair. Mutants deficient in excision repair, on the other hand, have no detected effect on the repair of transposition-induced lesions. These observations suggest that P element-induced lesions are repaired by a postreplication pathway of DNA repair. The data further support recent studies implicating double-strand DNA breaks as intermediates in P transposition, because the mei-41 gene has been genetically and cytologically associated with the repair of interrupted chromosomes. Analysis of this system has also revealed a striking stimulation of site-specific gene conversion and recombination by P transposition. This result strongly suggests that postreplication repair in this model eukaryote operates through a conversion/recombination mechanism. Our results also support a recently developed model for a conversion-like mechanism of P transposition (Engels et al., 1990). Involvement of the mei-41 and mus302 genes in the repair of P element-induced double-strand breaks and postreplication repair points to a commonality in the mechanisms of these processes.     

Recovery and characterization of hybrid dysgenesis-induced mei-9 and mei-41 alleles of Drosophila melanogaster

X-Linked methyl methanesulfonate (MMS)-sensitive mutations were induced with hybrid dysgenesis using four P strains: pi 2, Harwich, T-007 and OK-1. Mutations were identified after two generations of backcrosses to M strain females to replace the autosomes. Among 51,471 X-chromosomes examined 10 carried stable MMS-sensitive mutations representing 8 independent events. Males of the mutant strains failed to induce gonadal dysgenesis in crosses to Oregon-R females at 28.5 degrees C. Complementation tests showed that 3 of the induced mutations were mei-9 alleles, 2 were mei-41 alleles, 1 was a mus102 allele, and 2 were alleles at a newly identified MMS-sensitive locus, mus112 (map position: 1-32.8). As assayed by in situ hybridization on polytene chromosomes, each X-chromosome had no more than four P element insertions. 4 of the 8 mutations recovered in this study proved to have P element insertions at or very close to sites to which MMS sensitivity has been mapped. Hybrid dysgenesis-induced reversion of 2 mutants, mei-9RT1 and mei-41RT2, is associated with the loss of the P element from regions 4B and 14C respectively.     

Isolation and Characterization of X-Linked Mutants of DROSOPHILA MELANOGASTER Which Are Sensitive to Mutagens

Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41 (Baker and Carpenter 1972). Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102 , two to mus(1)103, and one each to mus(1)104, mus(1)105 , and mus(1)106). Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair ( Boyd and Setlow 1976). Only the mei-41 mutants are hypersensitive to UV radiation, although several of the mutants exhibit sensitivity to gamma-rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9.     

Genetic characterization of the mei-41 locus in Drosophila melanogaster

Summary The mutagen-sensitive mutant mus(1)104 ^D1 of Drosophila melanogaster maps to a position on the X chromosome very close to the meiotic mutant mei-41 ^D5 . Both mutants have been characterized as mutagen-sensitive and defective in post-replication repair. In the present report we show by complementation studies that mus(1)104 and mus(1)103 are allelic with mei-41. In addition, two reported alleles of mus(1)104 lie between the mei-41 alleles A10 and D5. The size of the mei-41 locus is estimated to be about 0.1 centimorgans (cM). Because several alleles of mei-41 have been shown to reduce recombination and increase meiotic chromosome loss and nondisjunction, mus(1)104 ^D1 females were examined for defects in meiosis. Although there was no evidence for reduced recombination on the second chromosome in homozygous mus(1)104 ^D1 females, heterozygous mus(1)104 ^D1 /mei-41 ^>D5 and mus(1)104 ^D1 /deficiency females showed reduced levels of recombination. However, there was no evidence of an increase in nondijunction in these females.We dedicate this article to the memory of Larry Sandler, who passed away suddenly on February 7, 1987     

Sensitivity of drosophila mutants to chemical carcinogens.

7 single-mutant and five double-mutant strains of Drosophila melanogaster were tested for their relative sensitivity to the chemical carcinogens: 1-acetylaminofluorene, benzo(alpha)pyrene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro quinoline-1-oxide and aflatoxin B1. Among the single mutants, mei-9a, mei-41D5 and mus(1)104D1 are hypersensitive to all 5 chemicals, whereas mus(1)107D1 is hypersensitive only to 4-nitroquinoline-1-oxide and is slightly sensitive to benzo(alpha)pyrene. The mei-9a mei-41D5 double-mutant is the most sensitive of 5 tested double-mutants which carry the mei-9a allele. When treated with 0.025 mM benzo(alpha)pyrene this double-mutant produces significantly more sex-linked recessive lethals and dominant lethals than does the control. Analysis of double-mutants reveals that the mei-9+ product functions in a different repair pathway of methyl methanesulfonate-induced damage than do the normal products of the mus(1)103, mus(1)104 and mus(1)107 loci. Our findings suggest that the sensitivity of Drosophila repair-deficient mutants could be exploited in screening for potential mutagens and carcinogens.     

A cell-cycle stage-related chromosomal X-ray hypersensitivity in larval neuroblasts of Drosophila mei-9 and mei-41 mutants suggesting defective DNA double-strand break repair

We have examined the chromosomal X-ray hypersensitivity in relation to the cell cycle in larval neuroblasts of the mutagen-sensitive and excision repair-defective mutant mei-9 and of the mutagen-sensitive and post-replication repair-defective mutant mei-41 of Drosophila melanogaster. When compared to wild-type cells, cells bearing the mei-9L1 allele produced unusually high levels in particular of chromatid deletions and to a lesser extent also of isochromatid deletions, but virtually no exchange aberrations. The chromosomal hypersensitivity is apparent at M1 when cells are irradiated in S or G2 but not when irradiated in G1. On the other hand, following irradiation cells bearing the mei-41D5 allele predominantly produce chromosome deletions. Also dicentric and chromatid exchange formation is enhanced with a moderate increase in chromatid deletions. The phases of major sensitivity are the S and G1. Mei-9 and mei-41 mutants have been classified to date as proficient in DNA double-strand break repair. The data presented in this paper revealed an S-independent clastogenic hypersensitivity of mei-9 and mei-41 cells. They are interpreted as indicative evidence for the presence of impaired DNA double-strand break repair. The cell-cycle-related difference in the ratio of chromatid- versus chromosome-type deletions in both mutants suggests repair defects at partially different phases of the cell cycle in mei-9 and mei-41 mutant cells.     

Postreplication repair-defective mutants of Drosophila melanogaster fall into two classes

Summary Primary cell cultures derived from embryos of a control stock of Drosophila melanogaster respond to ultraviolet light within the first hour after exposure with a decline in thymidine incorporation and a decline in the ability to form newly synthesized (nascent) DNA in long segments. Cells derived from two nonallelic excision-defective mutants (mei-9 and mus201) exhibit the same quantitative decline in both phenomena as do control cells. In contrast, cells from five nonallelic postreplication repair-defective mutants (mei-41, mus101, mus205, mus302 and mus310) respond to ultraviolet light by synthesizing nascent DNA in abnormally short segments. Two of these five mutants (mus302 and mus310) also exhibit unusually low thymidine incorporation levels after irradiation, whereas the other three mutants display the normal depression of incorporation.These results indicate that excision repair does not influence the amount or the length of nascent DNA synthesized in Drosophila cells within the first hour after exposure to ultraviolet light. Of the five mutations that diminish postreplication repair, only two reduce the ability of irradiated cells to synthesize normal amounts of DNA.Abbreviation used UV ultraviolet light — principal wavelength 254 nm     

The interaction of the rad201 gene with mei-9 and mei-41 genes in germline cells of Drosophila female

The effect of Drosophila mutation rad201G1 together with mutations mei-41D5 and mei-9a on the sensitivity of oocytes to induction of dominant lethals (DLs) was studied. To this end, the frequencies of spontaneous and gamma-radiation-induced DLs in consecutive egg batches of females carrying double or single mutations were estimated. Since the effects of the mutations examined are expressed only at the previtellogenetic stages of oogenesis, only newly hatched (0-5-hour-old) females, whose oocytes did not develop farther than stage 7, were irradiated. The results obtained indicated that in intact and irradiated oocytes of double mutants mei-9a rad201G1 and mei-41D5 rad201G1, mutation rad201G1 epistatically suppresses the mutations of the both mei genes.     

Induction of mutations in unirradiated X-chromosome of Drosophila melanogaster hybrids of repair deficient females mei-41 [D5] and mus209 [B1] and irradiated males M5

It has been analyzed the frequency of the recessive lethal mutations in the unirradiated X-chromosome of Drosophila. Females of wild type (CS) as well as of error-prone (mei-41) and error-free (mus209) mutant strains were used. In CS hybrids the increasing of the mutation rate (p < 0.05) was found. In muc209 hybrids the mutation rate was not affected. In mei-41 hybrids the tendency to decreasing of the mutation rate was found. The obtained results demonstrate the possible role of error-prone repair in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue.     

Genetic mechanisms of formation of radiation-induced instability of the genome and its transgenerational effects in the descendants of chronically irradiated individuals of Drosophila melanogaster

The article is devoted to the study of the role of intracellular mechanisms in the formation of radiation-induced genetic instability and its transgenerational effect in cells of different tissues of the descendants of Drosophila melanogaster mutant strains whose parents were exposed to chronic radiation (0.42 and 3.5 mGy/h). The level of DNA damage (alkali-labile sites (ALS), single-strand (SSB) and double-strand (DSB) breaks) in cells of somatic (nerve ganglia, imaginal discs) and generative (testis) tissues from directly irradiated animals and their unirradiated offspring was evaluated. Confident transgenerational instability (on the level of ALSs and SSBs), observed only in somatic tissues and only at the higher dose rate, is characteristic for mus209 mutant strains defective in excision repair and, less often, for mus205 and mus210 mutant strains. The greatest manifestation of radiation-induced genetic instability was found in evaluating the DSBs. Dysfunction of the genes mus205, mus304, mei-9 and mei-41, which are responsible for postreplicative repair, excision repair, recombination and control of the cell cycle, affects transgenerational changes in the somatic tissues of the offspring of parents irradiated in both low and high dose rates. In germ cells, the key role in maintaining genetic stability under chronic irradiation is played by the non-recombination postreplication repair mus101 gene. We revealed the tissue specificity of the radiation-induced effects, transgenerational transmission and accumulation of DNA damage to descendants of chronically irradiated animals.     

Drosophila mutations at the mei-9 and mus(2)201 loci which block excision of thymine dimers also block induction of unscheduled DNA synthesis by methyl methanesulfonate, ethyl methanesulfonate, N-methyl-N-nitrosourea, UV light and X-rays

The mei-9 and mus(2)201 mutants of Drosophila melanogaster were identified as mutagen-sensitive mutants on the basis of larval hypersensitivity to methyl methanesulfonate and characterized as excision repair-deficient on the basis of a greatly reduced capacity to excise thymine dimers from cellular DNA. The high degree of larval cytotoxicity observed with a variety of other chemical and physical agents indicated that these mutants may be unable to excise other important classes of DNA adducts. We have measured the ability of the single mutants and the double mutant combination mei-9;mus(2)201 to perform the resynthesis step in excision repair by means of an autoradiographic analysis of unscheduled DNA synthesis (UDS) induced in a mixed population of primary cells in culture. The 3 strains exhibit no detectable UDS activity in response to applied doses of 1.5-6.0 mM methyl methanesulfonate, 1.0-4.5 mM N-methyl-N-nitrosourea or 10-40 J/m2 254-nm UV light, dose ranges in which control cells exhibit a strong dose-dependent UDS response. The mei-9 and mei-9;mus(2)201 mutants also have no detectable UDS response to X-ray doses of 300-1800 rad, whereas the mus(2)201 mutant exhibits a reduced, but dose-dependent, response over this range. These data correlate well with the degree of larval hypersensitivity of the strains and suggest that mutations at both loci block the excision repair of a wide variety of DNA damage prior to the resynthesis step.     

The Effect of mei-41 on Rdna Redundancy in DROSOPHILA MELANOGASTER

The recombination and repair defective mutant, mei-41, exhibits three rather striking effects on the genetic properties and chromosomal stability of rDNA in Drosophila. First, mei-41 inhibits rDNA magnification. However, mei-9, another recombination and repair defective mutation has no similar effect. This indicates that magnification requires some, but not all, of the gene products necessary for meiotic exchange. Second, under magnifying conditions, mei-41 induces interchanges between the X rDNA and either arm of the Ybb- chromosome. These interchanges occur at high frequency and are independent of rDNA orientation. Third, in mei-41 bb+/Ybb+ males, bobbed mutants in the X, but not the Y, also arise at high frequency. Evidence suggests that these events involve the rDNA type I insertion. The recombination and repair defective properties of mei-41 together with our results regarding its unusual and specific effects involving rDNA are explained in a simple model that has general implications for chromosome structure.     

Studies on mutagen-sensitive strains of Drosophila melanogaster. VI. The effect of DNA-repair deficiencies in spermatids, spermatocytes and spermatogonia irradiated in N2 or O2

This study was aimed at ascertaining the extent to which paternal repair processes possibly deficient in mei-9a, mei-41D5 and mus-101D1 genotypes would affect the recovery of radiation-induced recessive lethals in early spermatids, spermatocytes and spermatogonia. These germ cell stages were sampled in two 2-day broods from freshly hatched males, that were irradiated as 24-h old pupae in O2, or N2 followed by N2 or O2 post-treatment. Spontaneous mutation frequencies were higher in mei-9 and mei-41 males, and thus appropriate corrections were applied to the radiation data. Only with mei-9 males a clear and consistent increase of the radiation-induced mutation frequency was observed. The effect is somewhat more pronounced in brood B, presumably representing spermatogonia, than in brood A and is observed after radiation in either O2 or N2. The paternal repair process thus differs from the maternal one in that it also responds to radiation damage induced in O2. The finding that, following irradiation under anoxia, post-treatment with O2 (versus that with N2), also lowers the mutation frequency in mei-9 males, indicates that the repair defect in mei-9 does not interfere with oxygen-dependent post-radiation repair. Thus there are two different paternal repair processes in these early stages of spermatogenesis: that is, one controlled by mei-9 and one depending on oxygen. Mei-41 and mus-101 do not appear to interfere with the paternal repair process. The frequency of translocations recovered from these stages was likewise not affected by mus-101.