The Centrosome and Its Duplication Cycle

Fu, Jingyan; Hagan, Iain; Glover, David M.

doi:10.1101/cshperspect.a015800

Cited by 210 publications

(204 citation statements)

References 333 publications

(405 reference statements)

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“…In human cells, a module of proteins that initiate centriole duplication in G 1 /S phase comprises CEP152 (named "asterless" in Drosophila), CEP63, and polo-like kinase 4 (PLK4) (60). This module assembles SAS6, CEP135, STIL, and CPAP into a platform, the so-called cartwheel (Fig.…”

Section: Centrin and Centrin-binding Proteins At Human Centrosomesmentioning

confidence: 99%

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Rüthnick

Schiebel

2016

Molecular and Cellular Biology

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bThe yeast spindle pole body (SPB) is the functional equivalent of the mammalian centrosome. Centrosomes and SPBs duplicate exactly once per cell cycle by mechanisms that use the mother structure as a platform for the assembly of the daughter. The conserved Sfi1 and centrin proteins are essential components of the SPB duplication process. Sfi1 is an elongated molecule that has, in its center, 20 to 23 binding sites for the Ca 2؉ -binding protein centrin. In the yeast Saccharomyces cerevisiae, all Sfi1 N termini are in contact with the mother SPB whereas the free C termini are distal to it. During S phase and early mitosis, cyclin-dependent kinase 1 (Cdk1) phosphorylation of mainly serine residues in the Sfi1 C termini blocks the initiation of SPB duplication ("off" state). Upon anaphase onset, the phosphatase Cdc14 dephosphorylates Sfi1 ("on" state) to promote antiparallel and shifted incorporation of cytoplasmic Sfi1 molecules into the half-bridge layer, which thereby elongates into the bridge. The Sfi1 C termini of the two Sfi1 layers localize in the bridge center, whereas the N termini of the newly assembled Sfi1 molecules are distal to the mother SPB. These free Sfi1 N termini then assemble the new SPB in G 1 phase. Recruitment of Sfi1 molecules into the anaphase SPB and bridge formation were also observed in Schizosaccharomyces pombe, suggesting that the Sfi1 bridge cycle is conserved between the two organisms. Thus, restricting SPB duplication to one event per cell cycle requires only an oscillation between Cdk1 kinase and Cdc14 phosphatase activities. This clockwork regulates the "on"/"off" state of the Sfi1-centrin receiver.T he mammalian centrosome and the yeast spindle pole body (SPB) are both able to nucleate microtubules (MTs) from tubulin subunits and are therefore collectively named MT organizing centers (MTOCs). A second common feature is the duplication of the centrosome and SPB just once during each cell division cycle. In each case, it is the mother centrosome or SPB that provides the platform for the assembly of the daughter (1-3).In yeast, the SPB is absolutely critical for mitotic spindle formation and chromosome segregation. This is because alternative MT assembly pathways, such as the RCC1/Ran-GTP-or augmindependent MT nucleation pathways, are absent from yeast (4, 5). In contrast, human cells can assemble a mitotic spindle even in the absence of centrosomes because of centrosome-independent MT formation and the presence of spindle assembly pathways. Recent studies have shown that the ability of human cells to tolerate loss of centrosomes or centrosome overduplication is reliant upon the inactivation of the p53 tumor suppressor gene that otherwise arrests these abnormal cells in G 1 phase (6, 7). How cells sense centrosome number defects is currently not understood. Yet it is becoming clearer why such a surveillance mechanism is important. Centrosome overamplification may contribute to cell transformation or enhance the aggressive nature of already transformed cells (8, 9). It is therefore...

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Section: Centrin and Centrin-binding Proteins At Human Centrosomesmentioning

confidence: 99%

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Rüthnick

Schiebel

2016

Molecular and Cellular Biology

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“…Centrosomes function in animal cells as microtubule-organizing centers to influence cell shape, polarity and motility, as well as spindle formation, chromosome segregation and cytokinesis 1–4 . Each centrosome typically comprises a pair of centrioles, which assemble a protein matrix, the pericentriolar material (PCM).…”

Section: Introductionmentioning

confidence: 99%

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Nigg

Holland

2018

Nat Rev Mol Cell Biol

419

546

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Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule related processes, including motility, cell division and cell signaling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each preexisting centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these structures contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit proliferation of cells with numerical centriole aberrations. Here we discuss recent progress in this field with a focus on signaling pathways and molecular mechanisms.

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“…In mitosis, a centrosome cell cycle exists to ensure spindle bipolarity. During S phase a centrosome duplicates and it is subsequently separated in M phase (Fu et al, 2015;Gonczy, 2015). However, there is a substantial difference in how the acentriolar meiotic spindle in mouse oocytes is regulated compared with the spindle in mitosis.…”

Section: Introductionmentioning

confidence: 99%

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

Balboula

Nguyen

Gentilello

et al. 2016

Journal of Cell Science

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Meiotic oocytes lack classic centrosomes and, therefore, bipolar spindle assembly depends on clustering of acentriolar microtubuleorganizing centers (MTOCs) into two poles. However, the molecular mechanism regulating MTOC assembly into two poles is not fully understood. The kinase haspin (also known as GSG2) is required to regulate Aurora kinase C (AURKC) localization at chromosomes during meiosis I. Here, we show that inhibition of haspin perturbed MTOC clustering into two poles and the stability of the clustered MTOCs. Furthermore, we show that AURKC localizes to MTOCs in mouse oocytes. Inhibition of haspin perturbed the localization of AURKC at MTOCs, and overexpression of AURKC rescued the MTOC-clustering defects in haspin-inhibited oocytes. Taken together, our data uncover a role for haspin as a regulator of bipolar spindle assembly by regulating AURKC function at acentriolar MTOCs in oocytes.

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The Centrosome and Its Duplication Cycle

Cited by 210 publications

References 333 publications

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

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