Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane

Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
The Journal of Cell Biology (Impact Factor: 9.83). 11/2012; 199(5):745-53. DOI: 10.1083/jcb.201208041
Source: PubMed


Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister chromatid segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in chromatid arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing chromatid arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)-depleted cells failed to elongate during segregation of long chromatids. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing chromatid arms and cortical myosin that ensures the clearance of chromatids from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity.

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    • "ensating for delays and defects in chromo - some segregation is particularly challenging . A number of studies demonstrate that some cells respond to delays in chromosome seg - regation by delaying initiation of cytokinesis ( Norden et al . , 2006 ) or alternatively elongating the spindle and daughter cells to accom - modate increased arm length ( Kotadia et al . , 2012 ) ."
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    ABSTRACT: To determine how chromosome segregation is coordinated with nuclear envelope formation (NEF), we examined the dynamics of NEF in the presence of lagging acentric chromosomes in Drosophila neuroblasts. Acentric chromosomes often exhibit delayed but ultimately successful segregation and incorporation into daughter nuclei. However, it is unknown whether these late segregating acentric fragments influence NEF to ensure their inclusion in daughter nuclei. Through live analysis, we show that acentric chromosomes induce highly localized delays in the reassembly of the nuclear envelope. These delays result in a gap in the nuclear envelope that facilitates the inclusion of lagging acentrics into telophase daughter nuclei. Localized delays of nuclear envelope reassembly require Aurora B kinase activity. In cells with reduced Aurora B activity, there is a decrease in the frequency of local nuclear envelope reassembly delays, resulting in an increase in the frequency of acentric-bearing lamin-coated micronuclei. These studies reveal a novel role of Aurora B for maintaining genomic integrity by promoting the formation of a passageway in the nuclear envelope through which late segregating acentric chromosomes enter the telophase daughter nucleus. © 2015 by The American Society for Cell Biology.
    Molecular biology of the cell 04/2015; 26(12). DOI:10.1091/mbc.E15-01-0026 · 4.47 Impact Factor
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    • "In addition, a stable bipolar structure is required to restrain separated chromatids in each daughter cell before cytokinesis, allow for spindle positioning during asymmetric divisions, and facilitate cytokinesis across the spindle midbody (Roostalu et al., 2010; Fededa and Gerlich, 2012; McNally, 2013). Anaphase spindle length has been observed to scale with cell size to various degrees in diverse organisms or cell types (Storchová et al., 2006; Hara and Kimura, 2009; Hu et al., 2011; Kotadia et al., 2012). Therefore, mechanisms likely exist that regulate the dynamics, elongation, and length of spindles during anaphase. "
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    ABSTRACT: Mitotic spindle function is critical for cell division and genomic stability. During anaphase, the elongating spindle physically segregates the sister chromatids. However, the molecular mechanisms that determine the extent of anaphase spindle elongation remain largely unclear. In a screen of yeast mutants with altered spindle length, we identified the kinesin-8 Kip3 as essential to scale spindle length with cell size. Kip3 is a multifunctional motor protein with microtubule depolymerase, plus-end motility, and antiparallel sliding activities. Here we demonstrate that the depolymerase activity is indispensable to control spindle length, whereas the motility and sliding activities are not sufficient. Furthermore, the microtubule-destabilizing activity is required to counteract Stu2/XMAP215-mediated microtubule polymerization so that spindle elongation terminates once spindles reach the appropriate final length. Our data support a model where Kip3 directly suppresses spindle microtubule polymerization, limiting midzone length. As a result, sliding forces within the midzone cannot buckle spindle microtubules, which allows the cell boundary to define the extent of spindle elongation.
    The Journal of Cell Biology 03/2014; 204(6). DOI:10.1083/jcb.201312039 · 9.83 Impact Factor
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    • "Studies analyzing C(2)EN syncytial embryos revealed that increased arm length resulted in an increased rate of errors in chromosome congression and segregation and loss of the damaged nuclei from the cortex (Sullivan et al. 1993). In contrast, a similar analysis in the slower dividing neuroblasts revealed that while the long C(2)EN chromosomes clearly lagged during anaphase, division failures did not occur (Gonzalez et al. 1991; Sullivan et al. 1993; Kotadia et al. 2012). Thus, the rapid maternally driven embryonic divisions were much more sensitive to division errors than were the later zygotic divisions. "
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    ABSTRACT: Among all organisms, Drosophila melanogaster has the most extensive well-characterized collection of large-scale chromosome rearrangements. Compound chromosomes, rearrangements in which homologous chromosome arms share a centromere, have proven especially useful in genetic-based surveys of the entire genome. However, their potential has not been fully realized because compound autosome stocks are refractile to standard genetic manipulations: if outcrossed, they yield inviable aneuploid progeny. Here we describe two strategies, cold-shock and use of the bubR1 mutant alleles, to produce nullo gametes through nondisjunction. These gametes are complementary to the compound chromosome-bearing gametes and thus produce viable progeny. Using these techniques, we created a compound chromosome two C(2)EN stock bearing a red fluorescent protein-histone transgene, facilitating live analysis of these unusually long chromosomes.
    G3-Genes Genomes Genetics 01/2013; 3(1):1-4. DOI:10.1534/g3.112.004481 · 3.20 Impact Factor
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