Academic journal article Genetics

Sustained and Rapid Chromosome Movements Are Critical for Chromosome Pairing and Meiotic Progression in Budding Yeast

Academic journal article Genetics

Sustained and Rapid Chromosome Movements Are Critical for Chromosome Pairing and Meiotic Progression in Budding Yeast

Article excerpt

ABSTRACT

Telomere-led chromosome movements are a conserved feature of meiosis I (MI) prophase. Several roles have been proposed for such chromosome motion, including promoting homolog pairing and removing inappropriate chromosomal interactions. Here, we provide evidence in budding yeast that rapid chromosome movements affect homolog pairing and recombination. We found that csm4Δ strains, which are defective for telomere-led chromosome movements, show defects in homolog pairing as measured in a "one-dot/two-dot tetR-GFP" assay; however, pairing in csm4Δ eventually reaches near wild-type (WT) levels. Charged-to-alanine scanning mutagenesis of CSM4 yielded one allele, csm4-3, that confers a csm4Δ-like delay in meiotic prophase but promotes high spore viability. The meiotic delay in csm4-3 strains is essential for spore viability because a null mutation (rad17Δ) in the Rad17 checkpoint protein suppresses the delay but confers a severe spore viability defect. csm4-3 mutants show a general defect in chromosome motion but an intermediate defect in chromosome pairing. Chromosome velocity analysis in live cells showed that while average chromosome velocity was strongly reduced in csm4-3, chromosomes in this mutant displayed occasional rapid movements. Lastly, we observed that spo11 mutants displaying lower levels of meiosis-induced double-strand breaks showed higher spore viability in the presence of the csm4-3 mutation compared to csm4Δ. On the basis of these observations, we propose that during meiotic prophase the presence of occasional fast moving chromosomes over an extended period of time is sufficient to promote WT levels of recombination and high spore viability; however, sustained and rapid chromosome movements are required to prevent a checkpoint response and promote efficient meiotic progression.

CELLS that enter meiosis undergo a single round of DNA replication followed by two divisions to yield haploid gametes, such as sperm and eggs in humans and spores in baker's yeast. Accurate segregation of chromosomes at the meiosis I (MI) and II (MII) divisions is a critical part of this process. Improper segregation can lead to aneuploidy, which in humans is a leading cause of infertility, miscarriages, and mental retardation (Hassold and Hunt 2001). One of the main causes of aneuploidy is nondisjunction of homologous chromosomes during MI. In most organisms, at least one crossover per homolog pair is essential for MI disjunction (Roeder 1997; Zickler and Kleckner 1999). Chromosome nondisjunction can occur if there are too few or too many crossovers or if crossovers are not properly placed, such as in close proximity to centromeres and telomeres (Hassold and Hunt 2001; Rockmill et al. 2006; Lacefield and Murray 2007). In the latter case, crossing over far from the centromere increases the likelihood of chromosomes segregating to the same spindle pole, resulting in aneuploidy (Lacefield and Murray 2007; Martinez-Perez and Colaiácovo 2009).

In baker's yeast, crossing over is initiated in meiosis by the formation of Spo11-dependent DNA double strand breaks (DSBs) (Keeney 2001). These breaks can be repaired as either crossovers or noncrossovers, with ~60% of the 140-170 DSBs processed as crossovers (Buhler et al. 2007; Mancera et al. 2008). In the interference- dependent crossover pathway, which leads to more widely spaced crossovers, DSBs are processed to form single-end invasion intermediates (SEIs) that result from the invasion of a DSB end into an intact homolog. These intermediates undergo second-end capture with the intact homolog to form double Holliday junctions (dHJs) that are ultimately resolved to form crossovers (Schwacha and Kleckner 1995; Allers and Lichten 2001; Börner et al. 2004; Lao et al. 2008).

During meiotic prophase in Saccharomyces cerevisiae, distinct chromosome motions are observed, which have been hypothesized to promote chromosome disjunction at MI. At the end of leptotene, telomeres attach to the nuclear envelope and move toward the spindle pole body, forming a bouquet-like structure (Trelles-Sticken et al. …

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