Meiotic Chromosome Behavior Influenced by Mutation-Altered Disjunction in DROSOPHILA MELANOGASTER Females

The effects of a female-specific meiotic mutation, altered disjunction (ald: 361), are described. Although ald females show normal levels of meiotic exchange, sex- and 4th-chromosome nondisjunction occurs at an elevated level. A large proportion of the nondisjunction events is the result of nonhomologous disjunction of the sex and 4th chromosomes. These nonhomologous disjunction events, and probably all nondisjunction events occurring in ald females, are the result of two anomalies in chromosome behavior: (1) X chromosomes derived from exchange tetrads undergo nonhomologous disjunction and (2) the 4th chromosomes nonhomologously disjoin from larger chromosomes. There is at best a marginal effect of ald on the meiotic behavior of chromosomes 2 or 3. The results suggest that the ald⁺ gene product acts to prevent the participation of exchange X chromosomes and all 4th chromosomes in nonhomologous disjunction events. The possible role of ald⁺ in current models of the disjunction process is considered.     

Survival ofDrosophila melanogaster Progeny after Prolonged Suppression of Pairing and Recombination in Autosome 3

Two laboratory strains of Drosophila melanogaster carrying autosome 3 with a meiotic mutation c(3)G, that is maintained since 1985 in various balancer chromosomes, were used to study progeny survival. The conditions of maintenance of these strains and the effect of c(3)G mutation completely suppress pairing and crossing over in autosome 3. In addition, selection pressure was reduced because of permanent heterozygosity, mediating mutation accumulation in the studied chromosome. In both strains, all homozygotes for autosome 3 (c(3)G/c(3)G) perished. The hybrid homozygotes carrying chromosomes with c(3)G mutation from different strains survived in 0.4 of the progeny. Higher viability was observed after normal pairing and meiotic recombination of the studied chromosome with the chromosome from the wild-type line. The possible nature of mutations accumulated after prolonged suppression of chromosome pairing and recombination is discussed.     

Orientation Disruptor (ord): A Recombination-Defective and Disjunction-Defective Meiotic Mutant in DROSOPHILA MELANOGASTER

The effects of a semidominant autosomal meiotic mutant, orientation disruptor (symbol: ord), located at 2–103.5 on the genetic map and in region 59B-D of the salivary map, have been examined genetically and cytologically. The results are as follows. (1) Crossing over in homozygous females is reduced to about seven percent of controls on all chromosomes, with the reduction greatest in distal regions. (2) Crossing over on different chromosomes is independent. (3) Reductional nondisjunction of any given chromosome is increased to about thirty percent of gametes from homozygous females. The probability of such nondisjunction is the same among exchange and nonexchange tetrads with the exception that a very proximal exchange tends to regularize segregation. (4) Equational nondisjunction of each chromosome is increased to about ten percent of gametes in homozygous females; this nondisjunction is independent of exchange. (5) The distributive pairing system is operative in homozygous females. (6) In homozygous males, reductional nondisjunction of each chromosome is increased to about ten percent, and equational nondisjunction to about twenty percent, of all gametes. (7) Cytologically, two distinct meiotic divisions occur in spermatocytes of homozygous males. The first division looks normal although occasional univalents are present at prophase I and a few lagging chromosomes are seen at anaphase I. However, sister chromatids of most chromosomes have precociously separated by metaphase II. Possible functions of the ord⁺ gene are considered.     

Meiosis in DROSOPHILA MELANOGASTER. III. the Effect of Orientation Disruptor (ord) on Gonial Mitotic and the Meiotic Divisions in Males

Orientation disruptor (ord), a meiotic mutant that is recombination defective in females and disjunction defective in males and females, has been analyzed using serial section electron and light microscopy. From analysis of primary spermatocytes we have confirmed that ord males are defective in some aspect of the mechanism(s) that holds sister chromatids together during meiosis. In addition, we have determined that ord causes high frequencies of nondisjunction during spermatogonial mitotic divisions, as well as during the meiotic divisions. Mitotic nondisjunction involves the large autosomes more frequently than the sex chromosomes or chromosome 4 and results in high frequencies of primary spermatocytes that are either monosomic or trisomic for chromosome 2 or 3. Abnormalities in spermatocyte cyst formation are also observed in males homozygous for ord. These abnormalities include loss of regulation of meiotic synchrony and the number of gonial cell divisions.     

Double or Nothing: A Drosophila Mutation Affecting Meiotic Chromosome Segregation in Both Females and Males

We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.     

A Meiotic Mutant Affecting Recombination in Female DROSOPHILA MELANOGASTER

mei-S282 is a female meiotic mutant isolated from a natural population of Drosophila melanogaster. It is a recessive mutation located at approximately map position 5 on the third chromosome which has two major effects. It causes a nonuniform decrease in recombination which is most drastic in distal chromosome regions and nondisjunction of all chromosome pairs is elevated at the first meiotic division. Nondisjunctional events are positively correlated; furthermore, nondisjoining chromosomes, themselves nonrecombinant, are preferentially recovered from cells in which nonhomologs are preferentially recovered from cells in which nonhomologs are also non-recombinant.-It is concluded that mei-S282 is a defect which occurs early in meiosis I prior to the time of exchange. In the mutant, the frequency of no-exchange tetrads for each of the major chromosomes is increased-and in cells which contain two or more no-exchange tetrads, an interaction between these chromosomes leads to correlated nondisjunction. mei-S282(+) then, is an exchange precondition necessary for the normal frequency and distribution of exchanges.     

The Utilization during Mitotic Cell Division of Loci Controlling Meiotic Recombination and Disjunction in DROSOPHILA MELANOGASTER

To inquire whether the loci identified by recombination-defective and disjunction-defective meiotic mutants in Drosophila are also utilized during mitotic cell division, the effects of 18 meiotic mutants (representing 13 loci) on mitotic chromosome stability have been examined genetically. To do this, meiotic-mutant-bearing flies heterozygous for recessive somatic cell markers were examined for the frequencies and types of spontaneous clones expressing the cell markers. In such flies, marked clones can arise via mitotic recombination, mutation, chromosome breakage, nondisjunction or chromosome loss, and clones from these different origins can be distinguished. In addition, meiotic mutants at nine loci have been examined for their effects on sensitivity to killing by UV and X rays.—Mutants at six of the seven recombination-defective loci examined (mei-9, mei-41, c(3)G, mei-W68, mei-S282, mei-352, mei-218) cause mitotic chromosome instability in both sexes, whereas mutants at one locus (mei-218) do not affect mitotic chromosome stability. Thus many of the loci utilized during meiotic recombination also function in the chromosomal economy of mitotic cells.—The chromosome instability produced by mei-41 alleles is the consequence of chromosome breakage, that of mei-9 alleles is primarily due to chromosome breakage and, to a lesser extent, to an elevated frequency of mitotic recombination, whereas no predominant mechanism responsible for the instability caused by c(3)G alleles is discernible. Since these three loci are defective in their responses to mutagen damage, their effects on chromosome stability in nonmutagenized cells are interpreted as resulting from an inability to repair spontaneous lesions. Both mei-W68 and mei-S282 increase mitotic recombination (and in mei-W68, to a lesser extent, chromosome loss) in the abdomen but not the wing. In the abdomen, the primary effect on chromosome stability occurs during the larval period when the abdominal histoblasts are in a nondividing (G2) state.—Mitotic recombination is at or above control levels in the presence of each of the recombination-defective meiotic mutants examined, suggesting that meiotic and mitotic recombination are under separate genetic control in Drosophila.—Of the six mutants examined that are defective in processes required for regular meiotic chromosome segregation, four (l(1)TW-6^cs, ca^nd, mei-S332, ord) affect mitotic chromosome behavior. At semi-restrictive temperatures, the cold sensitive lethal l(1)TW-6^cs causes very frequent somatic spots, a substantial proportion of which are attributable to nondisjunction or loss. Thus, this locus specifies a function essential for chromosome segregation at mitosis as well as at the first meiotic division in females. The patterns of mitotic effects caused by ca^nd, mei-S332, and ord suggest that they may be leaky alleles at essential loci that specify functions common to meiosis and mitosis. Mutants at the two remaining loci (nod, pal) do not affect mitotic chromosome stability.     

HorkaD, a Chromosome Instability-Causing Mutation in Drosophila, Is a Dominant-Negative Allele of lodestar

Correct segregation of chromosomes is particularly challenging during the rapid nuclear divisions of early embryogenesis. This process is disrupted by Horka^D, a dominant-negative mutation in Drosophila melanogaster that causes female sterility due to chromosome tangling and nondisjunction during oogenesis and early embryogenesis. Horka^D also renders chromosomes unstable during spermatogenesis, which leads to the formation of diplo//haplo mosaics, including the gynandromorphs. Complete loss of gene function brings about maternal-effect lethality: embryos of the females without the Horka^D-identified gene perish due to disrupted centrosome function, defective spindle assembly, formation of chromatin bridges, and abnormal chromosome segregation during the cleavage divisions. These defects are indicators of mitotic catastrophe and suggest that the gene product acts during the meiotic and the cleavage divisions, an idea that is supported by the observation that germ-line chimeras exhibit excessive germ-line and cleavage function. The gene affected by the Horka^D mutation is lodestar, a member of the helicase-related genes. The Horka^D mutation results in replacement of Ala777 with Thr, which we suggest causes chromosome instability by increasing the affinity of Lodestar for chromatin.     

The Meiotic Effects of a Deficiency in DROSOPHILA MELANOGASTER: Identification of Two Dosage-Sensitive Sites

Heterozygosity for a deficiency for the entire zeste-white region of the X chromosome of Drosophila melanogaster females causes both reduced recombination and increased nondisjunction. The location of the dosage-sensitive sites responsible for these two meiotic defects has been studied by use of a set of deficiencies that subdivide the region. Recombination is reduced when the zw7-zw11 region is present in one dose, while nondisjunction is increased only if the doses of both the zw8-zw10 and zw6-zw11 segments are reduced. Examination of trans heterozygotes of two deficiencies explicitly demonstrates the compound nature of the meiotic dose effect and further delimits the location of the proximal disjunctional site to the zw12-zw11 interval. In inversion/deficiency heterozygotes, reduced dose of the zw8-zw10 region alone, without reduced dose of the proximal site, yields increased nondisjunction, suggesting that the proximal element that affects disjunction is the same as that which affects recombination. Thus, the zeste-white region contains at least two dosagesensitive loci that affect meiosis: reduced dosage of one locus, in the zw7-zw11 interval, causes reduced recombination; reduced dose of another, in the zw8-zw10 region, increases the probability that nonexchange chromosomes will nondisjoin. A slight effect on the regional distribution of exchange may also be a property of the zw8-zw10 region locus, but could be an effect of yet another locus or of structural heterozygosity. The implications of these results for understanding meiotic control and the prospects for further analysis of the structure of the zeste-white interval are considered.     

The Genetic Analysis of Distributive Segregation in Drosophila Melanogaster. II. Further Genetic Analysis of the Nod Locus

In Drosophila melanogster females the segregation of nonexchange chromosomes is ensured by the distributive segregation system. The mutation noda specifically impairs distributive disjunction and induces nonexchange chromosomes to undergo nondisjunction, as well as both meiotic and mitotic chromosome loss. We report here the isolation of seven recessive X-linked mutations that are allelic to noda. As homozygotes, all of these mutations exhibit a phenotype that is similar to that exhibited by noda homozygotes. We have also used these mutations to demonstrate that nod mutations induce nonexchange chromosomes to nondisjoin at meiosis II. Our data demonstrate that the effects of noda on meiotic chromosome behavior are a general property of mutations at the nod locus. Several of these mutations exhibit identical phenotypes as homozygotes and as heterozygotes with a deficiency for the nod locus; these likely correspond to complete loss-of-function or null alleles. None of these mutations causes lethality, decreases the frequency of exchange, or impairs the disjunction of exchange chromosomes in females. Thus, either the nod locus defines a function that is specific to distributive segregation or exchange can fully compensate for the absence of the nod+ function.     

B Chromosome Nondisjunction in Corn: Control by Factors near the Centromere

B chromosomes of corn are stable at all mitotic and meiotic divisions of the plant except the second pollen mitosis. In the latter division, B chromosomes undego mitotic nondisjunction at rates as high as 98%. Studies by several workers on B-A translocation chromosomes have provided evidence for the existence of four factors on the B chromosome that control nondisjunction and are separable from the centromere. Two of these factors, referred to here as factors 3 and 4, flank the B chromosome centromere. Factor 3 is the centromere-adjacent heterochromatin in the long arm of the B chromosome; factor 4 is located in the minute short arm. Evidence is presented here supporting the existence of factors 3 and 4. Deficiencies that include each factor were identified following centromeric misdivision events, with breaks at or near the centromere of a B-translocation chromosome. B chromosomes lacking factors 3 or 4 show much less nondisjunction than do chromosomes containing them. The possible function of factor 4 in nondisjuntion is also discussed.     

Parameters of Male and Female Recombination Influenced by the T-007 Second Chromosome in DROSOPHILA MELANOGASTER

The T-007 second chromosome line of Drosophila melanogaster, previously shown to contain genetic elements responsible for male recombination induction, appears to affect several parameters of recombination in females. In T-007 heterozygous females, the distribution of recombination (but not the total frequency) is changed from that observed in control females; relative increases are observed in the more proximal regions of the second, third and X chromosomes, while relative decreases are observed more distally. These changes are paralleled by altered coefficient of coincidence values and in an increased nondisjunction frequency of second chromosomes. The distribution of recombination in females is strikingly similar to that observed in males as measured along the second and third chromosomes, and the frequency of nondisjunction of the X and Y chromosomes is increased in T-007 heterozygous males. Based upon these results and responses to the effect of structurally rearranged heterologues (the "interchromosomal effect"), it is suggested that T-007 affects the preconditions for meiotic exchange in females. It is not yet known if elements responsible for these effects are the same elements responsible for the numerous other traits associated with the T-007 second chromosome.     

Chromosome nondisjunction in <Emphasis Type="Italic">Drosophila</Emphasis> strains mutant for tumor suppressor Merlin

The effect of mutation for gene Merlin on chromosome disjunction in Drosophila during meiosis was genetically studied. Chromosome nondisjunction was not registered in females heterozygous for this mutation and containing structurally normal X chromosomes. In cases when these females additionally contained inversion in one of chromosomes X, a tendency toward the appearance of nondisjunction events was observed in individuals containing mutation in the heterozygote. The genetic construct was obtained allowing the overexpression of protein corresponding to a sterile allele Mer ³ in the germ cell line. This construct relieves the lethal effect of Mer ⁴ mutation. The ectopic expression of this mutant protein leads to chromosome nondisjunction in male meiosis.     

Genetic Analysis of Sex Chromosomal Meiotic Mutants in DROSOPHILA MELANOGASTER

A total of 209 ethyl methanesulfonate-treated X chromosomes were screened for meiotic mutants that either (1) increased sex or fourth chromosome nondisjunction at either meiotic division in males; (2) allowed recombination in such males; (3) increased nondisjunction of the X chromosome at either meiotic division in females; or (4) caused such females, when mated to males heterozygous for Segregation-Distorter (SD) and a sensitive homolog to alter the strength of meiotic drive in males.-Twenty male-specific meiotic mutants were found. Though the rates of nondisjunction differed, all twenty mutants were qualitatively similar in that (1) they alter the disjunction of the X chromosome from the Y chromosome; (2) among the recovered sex-chromosome exceptional progeny, there is a large excess of those derived from nullo-XY as compared to XY gametes; (3) there is a negative correlation between the frequency of sex-chromosome exceptional progeny and the frequency of males among the regular progeny. In their effects on meiosis these mutants are similar to In(1)sc(4L)sc(8R), which is deleted for the basal heterochromatin. These mutants, however, have normal phenotypes and viabilities when examined as X/0 males, and furthermore, a mapping of two of the mutants places them in the euchromatin of the X chromosome. It is suggested that these mutants are in genes whose products are involved in insuring the proper functioning of the basal pairing sites which are deleted in In(1)sc(4L)sc(8R), and in addition that there is a close connection, perhaps causal, between the disruption of normal X-Y pairing (and, therefore, disjunction) and the occurrence of meiotic drive in the male.-Eleven mutants were found which increased nondisjunction in females. These mutants were characterized as to (1) the division at which they acted; (2) their effect on recombination; (3) their dominance; (4) their effects on disjunction of all four chromosome pairs. Five female mutants caused a nonuniform decrease in recombination, being most pronounced in distal regions, and an increase in first division nondisjunction of all chromosome pairs. Their behavior is consistent with the hypothesis that these mutants are defective in a process which is a precondition for exchange. Two female mutants were allelic and caused a uniform reduction in recombination for all intervals (though to different extents for the two alleles) and an increase in first-division nondisjunction of all chromosomes. Limited recombination data suggest that these mutants do not alter coincidence, and thus, following the arguments of Sandler et al. (1968), are defective in exchange rather than a precondiiton for exchange. A single female mutant behaves in a manner that is consistent with it being a defect in a gene whose functioning is essential for distributive pairing. Three of the female meiotic mutants cause abnormal chromosome behavior at a number of times in meiosis. Thus, nondisjunction at both meiotic divisions is increased, recombinant chromosomes nondisjoin, and there is a polarized alteration in recombination.-The striking differences between the types of control of meiosis in the two sexes is discussed and attention is drawn to the possible similarities between (1) the disjunction functions of exchange and the process specified by the chromosome-specific male mutants; and (2) the prevention of functional aneuploid gamete formation by distributive disjunction and meiotic drive.     

A New Mapping Method Employing a Meiotic Rec- Mutant of Yeast

A rapid new mapping method has been developed for localizing a dominant or recessive mutation to a particular chromosome of yeast. The procedure utilizes the ability of strains homozygous for the spo11-1 mutation to undergo chromosome segregation without appreciable recombination during sporulation. The level of sporulation in spo11-1/spo11-1 diploids is reduced and asci are often immature or abnormal in appearance; spore viability is less than 1%. The first step of the mapping procedure is the construction of a haploid spo11-1 strain carrying a recessive drug-resistance marker and the unmapped mutation(s). This strain is crossed to a set of three spo11-1 mapping tester strains containing, among them, a recessive marker on each chromosome. The resulting spo11-1/spo11-1 diploids are sporulated and plated on drug-containing medium. Viable meiotic products that express the drug-resistance marker due to chromosome haploidization are selectively recovered. These meiotic products are haploid for most, but generally not all, chromosomes. The level of disomy for individual chromosomes averages 19%. Each of the recessive chromosomal markers is expressed in approximately a third of the drug-resistant segregants. Ninety-eight percent of these segregants show no evidence of intergenic recombination. Thus, two markers located on the same chromosome, but on different homologs, are virtually never expressed in the same drug-resistant clone. The utility of this mapping procedure is demonstrated by confirming the chromosomal location of seven known markers, as well as by the assignment of a previously unmapped mutation, spo12-1, to chromosome VIII. In addition, the analysis of the products of spo11-1 meiosis indicates that several markers previously assigned to either chromosome XIV or chromosome XVII are actually on the same chromosome.     

Cytogenetic Analysis of a Segment of the Y Chromosome of DROSOPHILA MELANOGASTER

Males carrying a large deficiency in the long arm of the Y chromosome known to delete the fertility gene kl-2 are sterile and exhibit a complex phenotype: (1) First metaphase chromosomes are irregular in outline and appear sticky; (2) spermatids contain micronuclei; (3) the nebenkerns of the spermatids are nonuniform in size; (4) a high molecular weight protein ordinarily present in sperm is absent; and (5) crystals appear in the nucleus and cytoplasm of spermatocytes and spermatids. In such males that carry Ste⁺ on their X chromosome the crystals appear long and needle shaped; in Ste males the needles are much shorter and assemble into star-shaped aggregates. The large deficiency may be subdivided into two shorter component deficiencies. The more distal is male sterile and lacks the high molecular weight polypeptide; the more proximal is responsible for the remainder of the phenotype. Ste males carrying the more proximal component deficiency are sterile, but Ste ⁺ males are fertile. Genetic studies of chromosome segregation in such males reveal that (1) both the sex chromosomes and the large autosomes undergo nondisjunction, (2) the fourth chromosomes disjoin regularly, (3) sex chromosome nondisjunction is more frequent in cells in which the second or third chromosomes nondisjoin than in cells in which autosomal disjunction is regular, (4) in doubly exceptional cells, the sex chromosomes tend to segregate to the opposite pole from the autosomes and (5) there is meiotic drive; i.e., reciprocal meiotic products are not recovered with equal frequencies, complements with fewer chromosomes being recovered more frequently than those with more chromosomes. The proximal component deficiency can itself be further subdivided into two smaller component deficiencies, both of which have nearly normal spermatogenic phenotypes as observed in the light microscope. Meiosis in Ste ⁺ males carrying either of these small Y deficiencies is normal; Ste males, however, exhibit low levels of sex chromosome nondisjunction with either deficient Y. The meiotic phenotype is apparently sensitive to the amount of Y chromosome missing and to the Ste constitution of the X chromosome.     

Survival of Drosophila melanogaster progeny after prolonged suppression of pairing and recombination in autosome 3

Two laboratory strains of Drosophila melanogaster carrying autosome 3 with a meiotic mutation c(3)G, that is maintained since 1985 in various balancer chromosomes, were used to study progeny survival. The conditions of maintenance of these strains and the effect of c(3)G mutation completely suppress pairing and crossing over in autosome 3. In addition, selection pressure was reduced because of permanent heterozygosity, mediating mutation accumulation in the studied chromosome. In both strains, all homozygotes for autosome 3 (c(3)G/c(3)G) perished. The hybrid homozygotes carrying chromosomes with c(3)G mutation from different strains survived in 0.4 of the progeny. Higher viability was observed after normal pairing and meiotic recombination of the studied chromosome with the chromosome from the wild-type line. The possible nature of mutations accumulated after prolonged suppression of chromosome pairing and recombination is discussed.     

A Cis-Acting Locus That Promotes Crossing over between X Chromosomes in Caenorhabditis Elegans

This study reports the characterization of a cis-acting locus on the Caenorhabditis elegans X chromosome that is crucial for promoting normal levels of crossing over specifically between the X homologs and for ensuring their proper disjunction at meiosis I. The function of this locus is disrupted by the mutation me8, which maps to the extreme left end of the X chromosome within the region previously implicated by studies of X;A translocations and X duplications to contain a meiotic pairing site. Hermaphrodites homozygous for a deletion of the locus (Df/Df) or heterozygous for a deletion and the me8 mutation (me8/Df) exhibit extremely high levels of X chromosome nondisjunction at the reductional division; this is correlated with a sharp decrease in crossing over between the X homologs as evidenced both by reductions in genetic map distances and by the presence of achiasmate chromosomes in cytological preparations of oocyte nuclei. Duplications of the wild-type region that are unlinked to the X chromosome cannot complement the recombination and disjunction defects in trans, indicating that this region must be present in cis to the X chromosome to ensure normal levels of crossing over and proper homolog disjunction. me8 homozygotes exhibit an altered distribution of crossovers along the X chromosome that suggests a defect in processivity along the X chromosome of an event that initiates at the chromosome end. Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs. This pairing center might function in the process of homolog recognition, or in the initiation of homologous synapsis.     

A Short Chromosomal Region with Major Roles in Yeast Chromosome III Meiotic Disjunction, Recombination and Double Strand Breaks

A multicopy plasmid was isolated from a yeast genomic library, whose presence resulted in a twofold increase in meiotic nondisjunction of chromosome III. The plasmid contains a 7.5-kb insert from the middle of the right arm of chromosome III, including the gene THR4. Using chromosomal fragments derived from chromosome III, we determined that the cloned region caused a significant, specific, cis-acting increase in chromosome III nondisjunction in the first meiotic division. The plasmid containing this segment exhibited high spontaneous meiotic integration into chromosome III (in 2.4% of the normal meiotic divisions) and a sixfold increase (15.5%) in integration in nondisjunctant meioses. Genetic analysis of the cloned region revealed that it contains a ``hot spot' for meiotic recombination. In DNA of rad50S mutant cells, a strong meiosis-induced double strand break (DSB) signal was detected in this region. We discuss the possible relationships between meiosis-induced DSBs, recombination and chromosome disjunction, and propose that recombinational hot spots may be ``pairing sites' for homologous chromosomes in meiosis.     

ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans

Crossover recombination and the formation of chiasmata normally ensure the proper segregation of homologous chromosomes during the first meiotic division. zhp-3, the Caenorhabditis elegans ortholog of the budding yeast ZIP3 gene, is required for crossover recombination. We show that ZHP-3 protein localization is highly dynamic. At a key transition point in meiotic prophase, the protein shifts from along the length of the synaptonemal complex (SC) to an asymmetric localization on the SC and eventually becomes restricted to foci that mark crossover recombination events. A zhp-3::gfp transgene partially complements a null mutation and reveals a separation of function; although the fusion protein can promote nearly wild-type levels of recombination, aneuploidy among the progeny is high, indicating defects in meiotic chromosome segregation. The structure of bivalents is perturbed in this mutant, suggesting that the chromosome segregation defect results from an inability to properly remodel chromosomes in response to crossovers. smo-1 mutants exhibit phenotypes similar to zhp-3::gfp mutants at higher temperatures, and smo-1; zhp-3::gfp double mutants exhibit more severe meiotic defects than either single mutant, consistent with a role for SUMO in the process of SC disassembly and bivalent differentiation. We propose that coordination of crossover recombination with SC disassembly and bivalent formation reflects a conserved role of Zip3/ZHP-3 in coupling recombination with SC morphogenesis.