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Meiotic Crossing Over Between Nonhomologous Chromosomes Affects Chromosome Segregation in Yeast

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Meiotic Crossing Over Between Nonhomologous Chromosomes Affects Chromosome Segregation in Yeast Copyright 0 1997 by the Cenetics Society of America Meiotic Crossing Over Between Nonhomologous Chromosomes Affects Chromosome Segregation in Yeast Sue Jinks-Robertson, Shariq Sayeed and Tamara Murphy Department of Biology, Emory University, Atlanta, Georgia 30322 Manuscript received August 27, 1996 Accepted for publication January 29, 1997 ABSTRACT Meiotic recombination between artificial repeats positioned on nonhomologous chromosomesoccurs efficiently in the yeast Saccharomyces cermisiae. Both gene conversion and crossover eventS have been observed, with crossovers yielding reciprocal translocations. In the current study, 5.5-kb uru3 repeats positioned on chromosomes V and XV were used to examine the effect of ectopic recombination on meiotic chromosome segregation. Urat randomspores were selected and gene conversion us. crossover events were distinguishedby Southern blotanalysis. Approximately 15% of the crossover events between chromosomesV and XV were associated with missegregationof one of these chromosomes. Themissegre- gation was manifest as hyperploid spores containing either both translocationsplus a normal chromo- some, or both normal chromosomes plus one of the translocations. In those cases where it could be analyzed, missegregation occurred at the first meiotic division. These data are discussed in terms of a model in which ectopic crossovers compete efficientlywith normal allelic crossovers in directing meiotic chromosome segregation. URING gamete formation insexually reproducing experience force in the opposing direction, and this D organisms, the process of meiosisreduces thedip- opposing force is provided by attachment of the recom- loid chromosome number and theDNA content by one- binationally linked homologue to the opposite pole of half so that subsequent gamete fusion restores the cor- the spindle (NICKLAS1974). Chiasmata are thecytologi- rect amount of genetic material in the zygote. In the cal manifestation of crossing over between homologues absence of such a specialized division, the genomecon- and in chiasmate organisms, mutations that eliminate tent would double with each generation. The meiotic or reduce meiotic crossing over are associated with the reduction of genetic material is achieved when a cell random segregation of homologues at MI. Available undergoes one round of chromosome replication fol- evidence thus indicates that crossing over generally is lowed by two successive nuclear divisions. The first of necessary for the proper disjunction of homologous these two meiotic divisions (meiosis I or MI) is reduc- chromosomes at MI (for reviews see BAKERet al. 1976; tional, with homologouschromosomes disjoining HAWLEY 1988), although some organisms have a back- and segregating to opposite poles of the spindle. The up distributive segregation system that can disjoin non- second meiotic division (meiosis I1 or MII) is equational recombinanthomologues (NILSSON-TILLGREN et al. and is formally analogous to a mitotic division, with 1986; HAWLEY et al. 1993). sister chromatids moving to opposite poles of the A second characteristic feature of meiosis is the for- spindle. mation of a distinct cytological structure that is absent A key genetic feature thatdistinguishes meiosis from in mitosis: the synaptonemal complex (SC; for a review vegetative mitotic divisions is the induction of very high see VONWETTSTEIN et al. 1984). The SC is a tripartite, levels of meiotic recombination. The meiotic recombi- proteinaceous structure that forms between paired ho- nation events occur after DNA replication but before mologous chromosomes before the first meiotic divi- MI, and consist of both nonreciprocal geneconversions sion. Given the similar temporal occurrence of genetic and associated crossovers.Meiotic crossing over not recombination and SC formation before MI, it was as- only generates novel, evolutionarily important combi- sumed for a number of years that SC formation facili- nations of alleles along a chromosome, butit also plays tated recombination by bringing homologous chromo- a critical role during gamete formation by facilitating somes into close register. According to this view, mei- the proper disjunctionof homologous chromosomes at otic recombination was absolutely dependent on and MI. Stable microtubule-mediated attachment of a chro- occurred after SC formation. mosome to one pole of the MI spindle requires that it The simplistic view of the relation between SC forma- tion and recombination has changed dramatically in recent years, due in large part to studies done in the Corresponding author: Sue Jinks-Robertson, Departmentof Biology, 1510 Clifton Rd., Emory University, Atlanta, GA 30322. yeast Saccharomyces cerwisiae (ATCHESONand ESPOSITO E-mail: [email protected] 1993; HAWLEY and ARBEL 1993). An early indication Genetics 146: 69-78 (Mav, 1997) 70 S. Jinks-Robertson, S. Sayeed and T. Murphy that the dependence of recombination on SC forma- find that ectopic crossing over between nonhomolo- tion between paired homologues might not be absolute gous chromosomes is accompanied by high levels of was the observation inyeast that homologous sequences missegregation of the chromosomes bearing the recom- positioned on nonhomologous chromosomes recom- bination substrates. Theseresults are discussed in terms bine efficiently in meiosis (ectopicrecombination; of the relation between meiotic crossing overand chro- JINKS-ROBERTSONand PETES1985, 1986; LICHTENet al. mosome disjunction at MI. 1987).The occurrence of ectopicinteractions sug- gested either that recombination could occur in the absence of SC, or that SC could form between short MATERIALS AND METHODS regions of homology embeddedin nonhomologous Strains, media and growth conditions: Diploid strains were chromosomes. Furthermore, itwas suggested that such obtained by mating SJR52 (MATcu his?::ura?-?,, ura?-50 Zeu2- ectopic recombination events might reflect a genome- ?,I12 his4 trpl,, ade2 metS-l,,; JINKS-ROBERTSONand PETES wide homology search that is responsible for chromo- 1986) with haploid MATa spores derived fromSJR59 (MATa/ some pairing and that precedes mature SC formation MATa his?/his?::ura?a,, his4/his4 ura3-5O/ura3-50 let&?, 112/ leu2-?,112 metS-l,Jmet &Iaf,, canl-l0l/canl a&2/ade2 trp/ (SMITHIESand 1986; CARPENTER 1987). Dou- POWERS trpl,, CEN-LEU2/CEN5; JINKS-ROBERTSONand PETES1986). ble-strandbreaks (DSBs) appear to be the initiating The following three spores wereused: SJR59-6b (MATa event for meiotic recombination (LIGHTEN and GOLD- his3::ura?-?,, ura?-50 CEN5-LEU2 leu2-3,1 12 his4 met8-l,,,, canl- MAN 1995)and detailed time-course analyses have 101), SJR59-1 Id (MATa hi~3::ura3-3~,,,ura?-50 CXN5-LEU2 shownthat these breaks occur before SC formation leu2-?,112 his4 met8-la, canl-101) and SJR.59-13b (MATa his3::ura?-3,,,, ura?-50 CEN5-LEU2 leu2-3,112 his4 trpl,, met8 (PADMORE et al. 1992). In addition, meiotic recombina- I,, canl-101). tion can occur in the absence of normal SC formation Diploid strains were grown vegetatively at 30" and were insome yeast mutants (HOLLINGSWORTHand BYERS sporulated at room temperature. Standard yeast media and 1989; ROCKMILLand ROEDER1990). genetic techniques were used (SHERMAN1991). YF'D (1%yeast If the SC is not essential for meiotic recombination, extract, 2% Bacto-peptone, 2% dextrose; 2.5% Bacto-agarfor plates) was used for nonselective growth. Recombinants were then what is its precise role inmeiosis? While this issue selected and nutritional markers scored on synthetic com- has not yet been fully resolved, there is evidence that plete(SC) drop-out plates, whichwere made by supple- the SC may impact on sister chromatid cohesion and menting synthetic minimal medium (0.17% yeast nitrogen hence may be important for chiasma maintenance(MA- base withoutamino acids and ammonium, 0.5% NH4S04,2% GUIRE 1990; MIYAZAKI andORR-WEAVER 1994). ENGE- dextrose, 2.5% agar) with all but the one relevant amino acid or base. SC-ura, for example, contained all amino acids and BRECHT et al. (1991) have presented evidence thatcross- adenine, but no uracil. For analysis of random spores, addi- overs occurring in the absence of SC in yeast fail to tional leucine (0.4 g/liter) was added to SC omission media direct the disjunction of homologous chromosomes at to avoid inadvertent selection against Leu- segregants. For MI, presumably because they fail to mature into chias- sporulation, diploid cells were pregrown inYF'A medium (1% mata. There is also evidence from yeast that the SC is yeast extract, 2% Bacto-peptone, 2% K-acetate) before trans- fer to sporulation medium (2% K-acetate) supplemented with importantfor the phenomenon of interference, in amino acids and bases required by the diploid. which a crossover inhibits the occurrence of additional Isolationand genetic characterization of Ura'random crossovers in nearby geneticintervals (SYMand ROEDER spores: Diploid strains were grown to -2 X lo7 cells/ml in 1994). 50 mlWA at 30". Cells were washed withHpO and appropriate While it is clear that crossovers between homologues volumesplated on SC-ura and WD to assess the mitotic frequency of Ura+ recombinants. The remaining cells were are important for disjunctionMI, at data from Drosoph- resuspended in sporulation medium at a density of - 1 X 10' ilafemales indicate that irradiation-induced meiotic cells/ml and incubated for 4-5 days at room temperature. crossovers ("interchanges") between nonhomologous For random spore analysis, sporulated cells were incubated chromosomes likewise can direct chromosome disjunc-
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