Centrosome instability: when good centrosomes go bad

Ryniawec, John M.; Rogers, Gerald S.

doi:10.1007/s00018-021-03928-1

Cited by 12 publications

(12 citation statements)

References 221 publications

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“…[40][41][42] When too many extra centrosomes are produced, the following steps further make the cell susceptible to CIN: (1) random attachment to the chromosome in the early stage of mitosis, creating a transient multipolar spindle; and (2) decomposing this abnormal mitotic configuration into a bipolar spindle. 43 This transition from multipolar spindles to bipolar spindles promotes the formation of incorrect kinetoplast-microtubule attachment, causing subsequent chromosome segregation errors in the late stage of division and forming aneuploid chromosomes during cytokinesis. The mechanism of tetraploid production also leads to the emergence of additional centrosomes, and has long been considered to be the pioneer of aneuploidy.…”

Section: Centrosome and Mitotic Spindle Defectsmentioning

confidence: 99%

Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect

Yan¹,

Liu²,

Liu³

2022

OTT

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As one of the first characteristics of cancer cells, chromosomal aberrations during cell division have been well documented. Aneuploidy is a feature of most cancer cells accompanied by an elevated rate of mis-segregation of chromosomes, called chromosome instability (CIN). Aneuploidy causes ongoing karyotypic changes that contribute to tumor heterogeneity, drug resistance, and treatment failure, which are considered predictors of poor prognosis. Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, and its genome map shows extensive aneuploid changes. Elucidating the role of aneuploidy in the pathogenesis of LC will reveal information about the key factors of tumor occurrence and development, help to predict the prognosis of cancer, clarify tumor evolution, metastasis, and drug response, and may promote the development of precision oncology. In this review, we describe many possible causes of aneuploidy and provide evidence of the role of aneuploidy in the evolution of LC, providing a basis for future biological and clinical research.

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Section: Centrosome and Mitotic Spindle Defectsmentioning

confidence: 99%

Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect

Yan¹,

Liu²,

Liu³

2022

OTT

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“…Defects in these processes can arise through the presence of too few or too many centrosomes, through inactive or overactive centrosomes, and even by changes in sub-organellar structure. Therefore, centrosomes must be tightly regulated to ensure they are intact and functional at the correct time and place (Nigg, 2018;Ryniawec, 2021;Schatten, 2018).…”

Section: Introductionmentioning

confidence: 99%

The UBR box E3 ligases Poe and Hyd are required for efficient Pericentrin degradation

Varadarajan

Galletta

Fagerstrom

et al. 2022

Preprint

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Centrosomes are the major microtubule organizing centers (MTOC) of many cells and are composed of centrioles and the pericentriolar material (PCM). Centrosomes are an essential part of diverse cellular processes and require precise regulation of their protein levels. One protein whose levels must be regulated is Pericentrin (PCNT in humans and PLP in Drosophila). Increased PCNT expression and its protein accumulation is linked to clinical conditions including cancer, mental disorders, and ciliopathies. However, the mechanisms by which PCNT levels are regulated remains underexplored. Our previous study (Galletta, 2020) demonstrated that PLP levels are sharply downregulated during early spermatogenesis and this regulation is essential to spatially position PLP on the proximal end of centrioles. We hypothesized that the sharp drop in PLP protein was a result of a rapid protein degradation during the male pre-meiotic G2 phase. In this study we show that the N-terminal region of PLP is required for regulating its levels, which when elevated, extends PLP position distally on centrioles. Consequently, PCM was also mispositioned leading to defects in spermatids. We then performed a targeted screen where we identified the E2 ligases, Rad6 and UbcD1, and the UBR box family E3 ligases, Poe (UBR4) and Hyd (UBR5) as factors that promote PLP degradation in spermatocytes. Collectively, our study suggests that Poe and Hyd directly bind the N-terminus of PLP and target it for degradation, ensuring proper centriole/basal body assembly and male fertility.

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“…The nuclei undergo extremely rapid syncytial divisions, forming the blastoderm. In addition to the microtubule-organizing roles, centrosomes serve as hubs for the integration and coordination of other biological processes ( Arquint et al 2014 ; Ryniawec and Rogers 2021 ). In syncytial Drosophila embryos, centrosomes attached to spindle poles are implicated in the spatial control of Cyclin B destruction, regulating the exit from mitosis ( Huang and Raff 1999 ; Wakefield et al 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Mitotic progression and dual spindle formation caused by spindle association of de novo–formed microtubule-organizing centers in parthenogenetic embryos of Drosophila ananassae

2022

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Facultative parthenogenesis occurs in many animal species that typically undergo sexual reproduction. In Drosophila, such development from unfertilized eggs involves diploidization after completion of meiosis, but the exact mechanism remains unclear. Here we used a laboratory stock of Drosophila ananassae that has been maintained parthenogenetically to cytologically examine the initial events of parthenogenesis. Specifically, we determined whether the requirements for centrosomes and diploidization that are essential for developmental success can be overcome. As a primal deviation from sexually reproducing (i.e., sexual) strains of the same species, free asters emerged from the de novo formation of centrosome-like structures in the cytosol of unfertilized eggs. Those microtubule-organizing centers (MTOCs) had distinct roles in the earliest cycles of parthenogenetic embryos with respect to mitotic progression and arrangement of mitotic spindles. In the first cycle, an anastral bipolar spindle self-assembled around a haploid set of replicated chromosomes. Participation of at least one MTOC in the spindle was necessary for mitotic progression into anaphase. In particular, the first mitosis involving a monastral bipolar spindle resulted in haploid daughter nuclei, one of which was associated with an MTOC whereas the other was not. Remarkably, in the following cycle, biastral and anastral bipolar spindles formed that were frequently arranged in tandem by sharing an aster with bidirectional connections at their central poles. We propose that, for diploidization of haploid nuclei, unfertilized parthenogenetic embryos utilize dual spindles during the second mitosis, as occurs for the first mitosis in normal fertilized eggs.

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Centrosome instability: when good centrosomes go bad

Cited by 12 publications

References 221 publications

Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect

Clinical Applications of Aneuploidies in Evolution of NSCLC Patients: Current Status and Application Prospect

The UBR box E3 ligases Poe and Hyd are required for efficient Pericentrin degradation

Mitotic progression and dual spindle formation caused by spindle association of de novo–formed microtubule-organizing centers in parthenogenetic embryos of Drosophila ananassae

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