Sequence of centromere separation: Occurrence, possible significance, and control

Vig, Baldev K.

doi:10.1016/0165-4608(83)90142-5

Cited by 56 publications

(22 citation statements)

References 46 publications

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“…9). Such differences in separase sensitivity would help explain the observation that sister chromatids separate in a specific order, as we observed in yeast and as previously observed in plant and animal cells 26,27 . The ordered segregation of chromatids provides a mechanism to maintain nuclear architecture through successive generations 27 .…”

supporting

confidence: 62%

Positive feedback sharpens the anaphase switch

Holt

Krutchinsky

Morgan

2008

Nature

173

182

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At the onset of anaphase, sister-chromatid cohesion is dissolved abruptly and irreversibly, ensuring that all chromosome pairs disjoin almost simultaneously. The regulatory mechanisms that generate this switch-like behavior are unclear. Anaphase is initiated when a ubiquitin ligase, the Anaphase-Promoting Complex (APC), triggers the destruction of securin, thereby allowing the protease, separase, to disrupt sister-chromatid cohesion 1-4. Here we demonstrate that Cdk1-dependent phosphorylation of securin near its destruction-box motif inhibits securin ubiquitination by the APC. The phosphatase Cdc14 reverses securin phosphorylation, thereby increasing the rate of securin ubiquitination. Because separase is known to activate Cdc14 5 , 6, our results support the existence of a positive feedback loop that increases the abruptness of anaphase. Consistent with this model, we show that mutations that disrupt securin phosphoregulation decrease the synchrony of chromosome segregation. Our results also suggest that coupling securin degradation with changes in Cdk1 and Cdc14 activities helps coordinate the initiation of sister-chromatid separation with changes in spindle dynamics.Securin is known to integrate multiple signaling pathways to delay anaphase in response to perturbations such as DNA damage 7,8 . We hypothesized that securin might also receive regulatory inputs that make separase activation more switch-like. To address this possibility, we used mass spectrometry to analyze the phosphorylation state of securin from mitotic budding yeast cells (Fig. 1a) 9 . We identified six phosphorylation sites, including four of the five sites corresponding to the consensus sequence of the cyclin-dependent-kinase, Cdk1 (S/ T*-P) (see also Suppl. Fig. 1). Three Cdk1 sites were found in securin's C-terminal domain, which is known to interact with separase 10 ; mutations at these sites are known to modulate securin's ability to bind separase and import it into the nucleus 11 . The fourth Cdk1 phosphopeptide, near the N terminus of securin, has not been characterized.The N-terminal Cdk1 site is near the destruction-box of securin, a motif important for recognition of substrates by the APC 2-4, 12 . To assess whether phosphorylation of this site affects securin ubiquitination by the APC, we tested the ability of purified APC to ubiquitinate purified securin before and after phosphorylation in vitro by Cdk1. We found that if securin was phosphorylated by Cdk1, the rate of ubiquitination by APC Cdc20 (the APC-activator complex that controls anaphase onset) was reduced 10-fold (Fig. 1b, c) and the rate of ubiquitination by APC Cdh1 was reduced 5-fold (Suppl. Fig. 2).This regulatory mechanism may be conserved -Drosophila and human homologues of securin have S/T-P motifs near their destruction-boxes, and both were ubiquitinated less efficiently by the APC after phosphorylation by Cdk1 (Suppl. Fig. 3 Cdc14 is a phosphatase that removes phosphates from Cdk1 substrates during anaphase and late mitosis 4,[13][14][15][16] . We found t...

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supporting

confidence: 62%

Positive feedback sharpens the anaphase switch

Holt

Krutchinsky

Morgan

2008

Nature

173

182

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“…In previous studies, cells of rapidly dividing tissues in the root tips also showed genome separation (Finch et al, 1981;Bennett 1988). Based on observations of metaphase cells in humans, Vig (1983) proposed that centromere separation is controlled by the amount of pericentromeric heterochromatin. However, both species of Torenia used in the present study possess almost the same amount of heterochromatin (Kikuchi et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Centromere separation and association in the nuclei of an interspecific hybrid between Torenia fournieri and T. baillonii (Scrophulariaceae) during mitosis and meiosis

et al. 2007

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In the nuclei of some interspecific hybrid and allopolyploid plant species, each genome occupies a separate spatial domain. To analyze this phenomenon, we studied localization of the centromeres in the nuclei of a hybrid between Torenia fournieri and T. baillonii during mitosis and meiosis using three-dimensional fluorescence in situ hybridization (3D-FISH) probed with species-specific centromere repeats. Centromeres of each genome were located separately in undifferentiated cells but not differentiated cells, suggesting that cell division might be the possible force causing centromere separation. However, no remarkable difference of dividing distance was detected between chromatids with different centromeres in anaphase and telophase, indicating that tension of the spindle fiber attached to each chromatid is not the cause of centromere separation in Torenia. In differentiated cells, centromeres in both genomes were not often observed for the expected chromosome number, indicating centromere association. In addition, association of centromeres from the same genome was observed at a higher frequency than between different genomes. This finding suggests that centromeres within one genome are spatially separated from those within the other. This close position may increase possibility of association between centromeres of the same genome. In meiotic prophase, all centromeres irrespective of the genome were associated in a certain portion of the nucleus. Since centromere association in the interspecific hybrid and amphiploid was tighter than that in the diploid parents, it is possible that this phenomenon may be involved in sorting and pairing of homologous chromosomes.

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“…Bivalents with smaller centromeres might tend to be delayed in congression and/or to lie in different places on the metaphase plate. Certainly, some chromosomes generally congress before others in various species (e.g., Vig, 1983). Results with intergeneric hybrids (Bennett, 1983;Finch and Bennett, 1983) have shown that one genome (set of chromosomes) has centromeres which are much less expressed (both by being smaller and having only approximately 10 per cent as many microtubules attached) than those of the other genome.…”

Section: Interaction Of Marked Bivalentsmentioning

confidence: 99%

Heteromorphic bivalent association at meiosis in bread wheat

1985

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Crosses were made between 51 different pairs of ditelocentric lines of hexaploid bread wheat (Triticum aestivum L.) to give double-monotelodisomic progeny with two different telocentric chromosomes. All the crosses involved pairs of chromosomes from the same genome.At meiosis, the two telocentric chromosomes paired with their normal homologous partners to form heteromorphic bivalents which could be distinguished from the other rod and ring bivalents at metaphase I-they were morphologically marked. The position which each marked bivalent occupied across the metaphase plate was scored in 5209 light-microscope equatorial squashes of pollen mother cells at metaphase I.There was a strong tendency for the marked bivalents to be positioned towards, or at, the outside edge of the plate. This occurred in all the hybrid lines, and showed that morphologically marked bivalents do not behave like their normal homologues, at least in this hexaploid species. However, the crosses involving marked chromosomes in the B genome tended to have the marked bivalents lying more often at the outside of the plate than did the crosses involving marked chromosomes from the A and D genome. Thus the genomes were behaving differently, and it is possible that the three genomes are spatially separated in the nucleus.

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Sequence of centromere separation: Occurrence, possible significance, and control

Cited by 56 publications

References 46 publications

Positive feedback sharpens the anaphase switch

Positive feedback sharpens the anaphase switch

Centromere separation and association in the nuclei of an interspecific hybrid between Torenia fournieri and T. baillonii (Scrophulariaceae) during mitosis and meiosis

Heteromorphic bivalent association at meiosis in bread wheat

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