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A Yeast Gene Required for the Segregation of Chromosomes During the Reductional Division of Meiosis BETH ROCKMILL and G

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A Yeast Gene Required for the Segregation of Chromosomes During the Reductional Division of Meiosis BETH ROCKMILL and G Proc. Natl. Acad. Sci. USA Vol. 85, pp. 6057-6061, August 1988 Genetics REDI: A yeast gene required for the segregation of chromosomes during the reductional division of meiosis BETH ROCKMILL AND G. SHIRLEEN ROEDER Department of Biology, Yale University, New Haven, CT 06511 Communicated by Gerald R. Fink, May 5, 1988 ABSTRACT A mutation at the RED) locus was identified nondisjunction at both meiotic divisions. The yeast mutants in a search for sporulation-proficient, meiotic-lethal yeast spol2 and spol3 are recombination-proficient and bypass the mutants. The few viable spores produced in the red)-) mutant first meiotic division (11). are highly aneuploid, suggesting that the spore lethality results To further analyze meiotic chromosome segregation in from a high frequency ofchromosome nondisjunction. Disomic yeast, we have devised a screen to identify meiotic-lethal spores produced by the red)-) mutant contain nonsister chro- mutants. Here we describe RED], a gene required for matids and the red)-) spore inviability phenotype is alleviated chromosome segregation during the first meiotic (reduc- in red)-) spo)3 double mutants; these results indicate that tional) division. nondisjunction occurs at the first meiotic division. The red)-) mutant is recombination-proficient. The REDI gene was cloned by complementation of the meiotic lethal phenotype; strains MATERIALS AND METHODS carrying a disruption of the gene are mitotically viable. We Yeast Strains. Yeast strains are listed in Table 1. The two propose that the RED) gene product is involved in meiosis I alleles arg4-8 and arg4-9 display temperature-sensitive, in- chromosome disjunction, perhaps by maintaining the connec- tragenic complementation (10). The arg4-8 allele is temper- tions between homologous chromosomes through metaphase I. ature-sensitive and displays a dosage effect; arg4-8 haploids are prototrophic up to 270C, whereas strains disomic for Meiosis is a special form of cell division responsible for the arg4-8 are prototrophic up to 30'C. Strains carrying the sexual phase of an organism's life cycle. Meiosis consists of arg4-9 allele are auxotrophic for arginine at all temperatures. two chromosome segregations generating haploid products Diploids or disomes heteroallelic for arg4-8 and arg4-9 are (gametes or spores) whose genomic content arises from an prototrophic up to 350C. The HIS4 alleles his4-280 and independent assortment of the recombined parental chromo- his4-290 also display intragenic complementation. The cyhlO- somes. During meiosis I, paired homologous chromosomes 100 allele was UV-induced and maps <0.5 centimorgan (cM) segregate from each other, reducing the diploid (2n) number from CEN2. of chromosomes to a haploid (in) set. It is this reductional Genetic Procedures. Media were prepared and yeast ma- division that distinguishes meiosis from mitosis. In the nipulations were carried out according to Sherman et al. (12). meiosis II equational division, sister chromatids segregate YEPAD medium is YEPD medium supplemented with ade- from each other as in mitosis. nine. Copper-containing medium is synthetic complete me- Little is known about the mechanism of reductional chro- dium (SC medium) made with 1.5% Phytagar (GIBCO); mosome segregation (ref. 1, for review). In chiasmate organ- CuS04 was added after autoclaving. To select spore colonies isms, the proper segregation of chromosomes during meiosis resistant to copper, sporulated patches of cells were repli- appears to require the pairing of homologous chromosomes cated to SC + cup (SC medium plus added CUS04 to 0.1 mM). (synapsis) and at least one genetic exchange per chromosome UV mutagenesis (to 50% survival) was carried out on spores (2). Asynaptic mutants in plants (reviewed in ref. 3) have a that had been treated with Zymolyase 100T, sonicated, and reduced frequency of paired homologous chromosomes at plated on solid YEPAD medium. Yeast transformations were pachytene and display high levels of meiosis I nondisjunc- carried out according to Sherman et al. (12); transformants tion. Mutants at the HOPI locus of Saccharomyces cerevi- were analyzed by Southern blot hybridization to confirm that siae (N. Hollingsworth and B. Byers, personal communica- substitution had occurred as expected. tion) are defective in the pairing ofhomologous chromosomes; Ether Test for Spore Viability. Sporulated patches of cells these mutants display reduced levels of recombination and were replica-plated to YEPAD medium in glass Petri dishes. produce inviable spores. Yeast mutants that completely abol- A 4 cm x 4 cm square of Whatman no. 1 filter paper, ish recombination, such as spoll (4) and rad5O (5), also saturated with 0.5 ml of diethyl ether, was placed in the lid of produce inviable meiotic products, presumably due to high each inverted dish. The Petri dishes were placed in an levels of aneuploidy. These observations imply that meiotic ether-resistant plastic box with a beaker containing several recombination is required for the reductional segregation of milliliters of ether. The box was sealed with a lid and chromosomes. incubated for 15 min; another 0.5 ml of ether was then added Synapsis and recombination do not ensure proper segre- to each dish and the plates were incubated for another 15 min. gation at meiosis I. Meiotic mutants have been identified that The filter paper was then removed from each dish and the are recombination-proficient but defective in chromosome plates were set, with lids ajar, to dry in a hood for 45 min. segregation. For example, desynaptic mutants in maize Plates were scored after 24 hr. undergo normal levels of exchange, yet homologs segregate aberrantly at meiosis I anaphase (6). In addition, the Dro- RESULTS sophila mutants ord, meiS332, and G67 (3, 7-9) and the yeast mutant DISJ (10) are recombination-proficient but undergo Isolation of the red)-) Mutant. In designing a screen for mutants defective in meiotic chromosome transmission, we The publication costs of this article were defrayed in part by page charge reasoned that such mutants would form spores but these payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. Abbreviation: cM, centimorgan(s). 6057 Downloaded by guest on September 29, 2021 6058 Genetics: Rockmill and Roeder Proc. Natl. Acad. Sci. USA 85 (1988) Table 1. Yeast strains Strain Genotype MATa his4-290 HO trpl-) arg4-8 thrl-4 ura3-1 BR1824-2B MATa his4-290 HO trpl-) arg4-8 thrl-4 ura3-1 MATa leu2 his4-290 red)-) arg4-8 THRI trpl-) ura3-1 cyh)0-100 BR2140 MATa LEU2 his4-280 red)-) arg4-9 thrl trpl-289 URA3 CYHIO MATa leu2 his4-290 RED) arg4-8 THRI trpl-) ura3-1 cyh)0-100 BR2142 MATa LEU2 his4-280 redl-) arg4-9 thrl trpl-289 URA3 CYHIO MATa leu2-27 his4-260, 519 RED) trpl-) spo)3::URA3 ura3-1 BR2327 MATa LEU2 his4-280 red)-) trpl-289 spol3::URA3 ura3-J MATa leu2-27 his4-260, S19 redl-) trpl-) spo)3::URA3 ura3-1 BR2328 MATa LEU2 his4-280 redl-) trpl-289 spol3::URA3 ura3-1 MATa leu2-27 his4-280 cyhl0-100 red)-) arg4-8 trpl-l ura3-1 BR2344 MATa LEU2 his4-280 CYHIO redl::Tn2Oarg4-9trpl-289ura3-1 MATa leu2-27 HIS4 ura3-1 redl-l trpl-) spol3::URA3 BR2354 MATa LEU2 his4-280 ura3-1 redl-) trpl-289 spol3::URA3 MATa leu2-27 HIS4 RED] trpl-) spol3::URA3 ura3-1 BR2371 MATa LEU2 his4-280 red)-) trpl-289 spol3::URA3 ura3-1 MATa his4-280 arg4-8 trpl-) cyh)0-)00 ura3-1 BR2408 MATa his4-290 arg4-9 TRPI CYHIO ura3-1 All genotypes are heterothallic (ho), RED), and CUP)P unless otherwise indicated. The allele redl::Tn2O (strain BR2344) was constructed by transposon mutagenesis. meiotic products would be highly aneuploid and therefore chromosome III with MATa and MATa and by the comple- inviable. Thus, a screen for sporulation-proficient, meiotic- menting alleles his4-280 and his4-290. Chromosome VIII was lethal mutants was employed. To recover recessive mutants marked with the complementing alleles arg4-8 and arg4-9. in a diploid strain, spores from a homothallic (HO) strain Physically isolated spores (15) were obtained from sporulated were mutagenized (3). Homothallic haploid spores switch cultures and plated on cycloheximide-containing medium. mating type within the first few cell divisions and then mate The Red+ diploid produced a low frequency of His+ and to form diploids homozygous for any induced mutations (13). Arg+ colonies (Table 2) and these were haploids resulting Because yeast does not sporulate with 100% efficiency, from intragenic recombination (data not shown). The diploid spore viability cannot be assessed simply by examining the homozygous for red)-) produced spores that were 38% growth of a sporulated culture. The growth of unsporulated histidine prototrophs, 33% arginine prototrophs, and 34% cells would obscure the reduction in spore viability. To nonmaters (Table 2). These results demonstrate high levels of overcome this problem, we took advantage of the observa- aneuploidy among the survivors of meiosis in the red)-) tion that vegetative cells are more sensitive than spores to mutant. Thus, the spore inviability observed in the red)-) killing by diethyl ether (14). Thus, the viability of spores is mutant is probably the result of meiotic nondisjunction. indicated by growth on rich medium after exposure to ether Disomic Spores Are the Products of Meiosis I Nondisjunc- vapors (see Materials andMethods). Spores from the diploid tion. To determine whether the nondisjunction caused by a BR1824-2B were mutagenized by UV, and diploid colonies red) mutation occurs during meiosis I and/or meiosis II, incapable of growth after sporulation and exposure to ether chromosome VIII disomes were selected and analyzed for were scored for the production ofvisible asci. Those colonies the presence of sister or nonsister chromosomes. Chromo- that sporulated were examined by tetrad dissection to con- some VIII disomes can be selected on the basis of copper firm the spore inviability phenotype.
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