Chromosome Segregation in Mitosis and Meiosis

Murray, Andrew W.; Szostak, Jack W.

doi:10.1146/annurev.cb.01.110185.001445

Cited by 189 publications

(113 citation statements)

References 62 publications

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“…Meiotic crossing over has a well demonstrated role in the faithful segregation of homologous chromosomes (1,(17)(18)(19); homologs not connected by crossovers in meiotic prophase often fail to attach stably to the meiotic spindle, and consequently may be distributed randomly to the daughter cells. Thus by promoting crossovers r ϩ alleles will increase fertility, and this advantage might allow them to persist in spite of their loss by conversion in heterozygotes.…”

Section: Resultsmentioning

confidence: 99%

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The hotspot conversion paradox and the evolution of meiotic recombination

Boulton

Myers²,

Redfield

1997

Proc. Natl. Acad. Sci. U.S.A.

174

199

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Studies of meiotic recombination have revealed an evolutionary paradox. Molecular and genetic analysis has shown that crossing over initiates at specific sites called hotspots, by a recombinational-repair mechanism in which the initiating hotspot is replaced by a copy of its homolog. We have used computer simulations of large populations to show that this mechanism causes active hotspot alleles to be rapidly replaced by inactive alleles, which arise by rare mutation and increase by recombination-associated conversion. Additional simulations solidified the paradox by showing that the known benefits of recombination appear inadequate to maintain its mechanism. Neither the benefits of accurate segregation nor those of recombining f lanking genes were sufficient to preserve active alleles in the face of conversion. A partial resolution to this paradox was obtained by introducing into the model an additional, nonmeiotic function for the sites that initiate recombination, consistent with the observed association of hotspots with functional sites in chromatin. Provided selection for this function was sufficiently strong, active hotspots were able to persist in spite of frequent conversion to inactive alleles. However, this explanation is unsatisfactory for two reasons. First, it is unlikely to apply to obligately sexual species, because observed crossover frequencies imply maintenance of many hotspots per genome, and the viability selection needed to preserve these would drive the species to extinction. Second, it fails to explain why such a genetically costly mechanism of recombination has been maintained over evolutionary time. Thus the paradox persists and is likely to be resolved only by significant changes to the commonly accepted mechanism of crossing over.Meiotic crossing over between homologous chromosomes plays two important roles in the genetic reshuffling caused by sexual reproduction: it creates new combinations of alleles within each chromosome, and it prevents nondisjunction during chromosome segregation (1). Crossovers are initiated primarily at specific sites called hotspots (2, 3). Most studies of the mechanism have been done in ascomycete fungi, where meiosis can be synchronously induced and all the meiotic products recovered in the ascus. Biased gene conversion is a typical consequence of recombination at hotspots (4-6). For example, a cross between active and inactive alleles of the ARG4 hotspot in the yeast Saccharomyces cerevisiae exhibits a 22-fold bias toward conversion of the active allele to its inactive homolog (6). Physical studies have shown that recombination events in S. cerevisiae are initiated by site-specific doublestrand DNA breaks at hotspots, before the visible pairing of the chromosomes (7, 8). As illustrated in Fig. 1, these breaks are thought to be repaired by DNA synthesis that uses the strands of the homologous chromosomes as templates, with resolution of the repair intermediate frequently creating a crossover between the participating chromosomes (9, 10). This and rela...

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Section: Resultsmentioning

confidence: 99%

“…Meiotic crossing over between homologous chromosomes plays two important roles in the genetic reshuffling caused by sexual reproduction: it creates new combinations of alleles within each chromosome, and it prevents nondisjunction during chromosome segregation (1). Crossovers are initiated primarily at specific sites called hotspots (2,3).…”

mentioning

confidence: 99%

The hotspot conversion paradox and the evolution of meiotic recombination

Boulton

Myers²,

Redfield

1997

Proc. Natl. Acad. Sci. U.S.A.

174

199

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“…If these three sets of results are combined, then some tentative conclusions can be drawn about kinetochore position during the cell cycle in S. cerevisiae. Since S. cerevisiae, like Saprolegnia, has nuclear microtubules attached to the SPB during interphase, then, as in Saprolegnia (Heath, 1980a), kinetochores may also be attached to these microtubules in interphase S. cerevisiae as proposed by Murray and Szostak (1985). During SPB replication, assuming S. cerevisiae is like Saprolegnia (Heath and Rethoret, 1981), the pre-existing kinetochores would be shared between the two SPBs and remain closely attached to them, a short spindle would form, and shortly after this kinetochore replication could take place.…”

Section: Localization Of Ndcl0pmentioning

confidence: 99%

NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae

Goh¹,

Kilmartin²

1993

Trends in Cell Biology

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“…13 and unpublished result). (2) pSS161 strongly hybridizes to the PFG gel electrophoretic band of an S. p mini-chromosome Chl6 (19) shown). Only one cosmid DD7 hybridizes to pSS162 (Figure 5c), indicating that a part of dhI (and dhII) is missing in certain dhIII sequences.…”

Section: Identification Of a Novel Centromeric Sequence In S Pombementioning

confidence: 97%

“…The centromere is a functional domain of chromosomes, the attachment site for kinetochore microtubules which radiate from the centrosomes to separate the chromosomes during mitosis (1)(2)(3)(4). The centromere is also the site for sister chromatid association.…”

Section: Introductionmentioning

confidence: 99%

A novel sequence common to the centromere regions ofSchizosaccharomyces pombechromosomes

1987

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An approximately 4 kb long sequence (designated dh) is located in the centromere regions of all three chromosomes of S. pombe. There is one copy each of dh per centromere in chromosomes I and II and multiples in the centromere of chromosome III. Nucleotide sequence determination shows that dhI and dhII are highly homologous. A part of the sequence (ca. 300-400 bp) contains short direct repeats, otherwise dh is in general internally nonrepetitious. Although there are three segmental deletions (total 821 bp) and two insertions (27 bp) in dhII (an 80% overall homology to dhI), there are only nine substitutions between dhI and dhII in the remaining 3980 bp, giving a 99.77% homology. The substitutions are restricted to the non-repetitious domains and are only of the pyrimidine-pyrimidine or purine-purine types. A possible conformational role of dh is discussed. INTRODUCTIONThe centromere is a functional domain of chromosomes, the attachment site for kinetochore microtubules which radiate from the centrosomes to separate

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Chromosome Segregation in Mitosis and Meiosis

Cited by 189 publications

References 62 publications

The hotspot conversion paradox and the evolution of meiotic recombination

The hotspot conversion paradox and the evolution of meiotic recombination

NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae

A novel sequence common to the centromere regions ofSchizosaccharomyces pombechromosomes

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