Cytokinesis: Placing and Making the Final Cut

Barr, Francis A.; Grüneberg, Ulrike

doi:10.1016/j.cell.2007.11.011

Cited by 433 publications

(482 citation statements)

References 128 publications

(202 reference statements)

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“…Cytokinesis is a highly complicated process, requiring delicate coordination between many players (Barr and Gruneberg, 2007), and it is not yet clear which of the components are the targets of Nek7 kinase. One possible target is the microtubule network as several studies demonstrate the involvement of NIMA kinases in microtubule-related activities (O'Connell et al, 2003;O'Regan et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Nek7 kinase targeting leads to early mortality, cytokinesis disturbance and polyploidy

et al. 2010

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The mammalian NIMA-related kinases (Neks) are commonly referred to as mitotic kinases, although a definitive in vivo verification of this definition is largely missing. Reduction in the activity of Nek7 or its close paralog, Nek6, has previously been shown to arrest cells in mitosis, mainly at metaphase. In this study, we investigate the developmental and cellular roles of Nek7 kinase through the generation and analysis of Nek7-deficient mice. We show that absence of Nek7 leads to lethality in late embryogenesis or at early post-natal stages and to severe growth retardation. Mouse embryonic fibroblasts (MEFs) derived from Nek7 À/À embryos show increase tendency for chromosomal lagging, micronuclei formation and cytokinesis failure. Tetraploidy and aneuploidy were commonly observed and their prevalence arises with MEFs passages. The frequency of multicentrosomal cells in the mutant's MEF cells was higher, and it commonly occurred concurrently with a binuclear phenotype, suggesting cytokinesis failure etiology. Lastly, the percentage of mutant MEF cells bearing primary cilia (PC) was low, whereas a cell population having two cilia appeared in the mutant MEFs. Taken together, these results confirm Nek7 as a regulator of cell division, and reveal it as an essential component for mammalian growth and survival. The intimate connection between tetraploidy, aneuploidy and cancer development suggests that Nek7 deregulation can induce oncogenesis.

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Section: Discussionmentioning

confidence: 99%

Nek7 kinase targeting leads to early mortality, cytokinesis disturbance and polyploidy

et al. 2010

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“…Following the separation of sister chromatids, a nuclear envelope re-assembles around each set of segregated chromatin (telophase). The cell cycle is terminated after the evolutionally conserved process of cytokinesis, which comprises the following major events (Guertin et al, 2002;Barr and Gruneberg, 2007).…”

Section: Centrosome Sister Chromatidmentioning

confidence: 99%

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Smith¹,

Dejsuphong

Balestrini³

et al. 2009

Nat Cell Biol

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The effects of ATM and ATR signalling induced by chromosomal breakage have been described extensively in modulating cell cycle progression up to the onset of mitosis.However, DNA damage checkpoint responses in mitotic cells are not well understood.This thesis reports on the effects of double strand breaks on the progression of mitosis.We found ATM and ATR activation can occur in mitotic Xenopus laevis egg extract and the induction of ATM and ATR by chromosomal breakages inhibits spindle assembly in both Xenopus egg extract and somatic cells. The delay in mitotic progression induced by ATM and ATR was found not to involve major spindle assembly factors activities such as, Cdk1, Plx1 and RCC1/Ran-GTP. However, normal anastral spindles formation around linear DNA coated beads, which can activate ATM and ATR, linked centrosome-driven spindle assembly to ATM and ATR dependent spindle defects. cDNA expression library screening was undertaken to identify novel ATM and ATR targets in this mitotic checkpoint pathway, through which the novel centrosomal protein XCEP63 was identified as a likely candidate. Data obtained from depletion and reconstitution of XCEP63 in Xenopus egg extract established that normal centrosome-driven spindle assembly requires XCEP63. Moreover, ATM and ATR phosphorylates XCEP63 on serine 560 and promotes delocalisation from the centrosome. ATM and ATR inhibition or addition of non-phosphorylable XCEP63 recombinant protein mutated at serine 560 prevents spindle assembly abnormalities.These findings suggest that ATM and ATR regulate mitotic events by targeting XCEP63 and centrosome-dependent spindle assembly. This pathway may provide support for DNA repair processes or regulate cell survival in the presence of mitotic DNA damage. 3

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“…Successful mitotic exit and cytokinesis rely on several key events. These include the timely onset of anaphase, triggered by cyclin degradation and consequent inactivation of Cdk1, as well as the formation of a central spindle, followed by assembly of an actomyosin ring beneath the cell cortex, ingression of the cleavage furrow and, finally, abscission [118]. The role of the mammalian centrosome in these late mitotic events is incompletely understood, but several intriguing observations have been reported.…”

Section: Centrosomes As Signalling Platforms In Vertebrates? (A) Cellmentioning

confidence: 99%

Centrosomes as signalling centres

Arquint

Gabryjonczyk

Nigg

2014

Phil. Trans. R. Soc. B

133

114

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Centrosomes—as well as the related spindle pole bodies (SPBs) of yeast—have been extensively studied from the perspective of their microtubule-organizing roles. Moreover, the biogenesis and duplication of these organelles have been the subject of much attention, and the importance of centrosomes and the centriole–ciliary apparatus for human disease is well recognized. Much less developed is our understanding of another facet of centrosomes and SPBs, namely their possible role as signalling centres. Yet, many signalling components, including kinases and phosphatases, have been associated with centrosomes and spindle poles, giving rise to the hypothesis that these organelles might serve as hubs for the integration and coordination of signalling pathways. In this review, we discuss a number of selected studies that bear on this notion. We cover different processes (cell cycle control, development, DNA damage response) and organisms (yeast, invertebrates and vertebrates), but have made no attempt to be comprehensive. This field is still young and although the concept of centrosomes and SPBs as signalling centres is attractive, it remains primarily a concept—in need of further scrutiny. We hope that this review will stimulate thought and experimentation.

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Cytokinesis: Placing and Making the Final Cut

Cited by 433 publications

References 128 publications

Nek7 kinase targeting leads to early mortality, cytokinesis disturbance and polyploidy

Nek7 kinase targeting leads to early mortality, cytokinesis disturbance and polyploidy

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Centrosomes as signalling centres

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