The mammalian centrosome and its functional significance

Schatten, Heide

doi:10.1007/s00418-008-0427-6

Cited by 120 publications

(102 citation statements)

References 202 publications

(226 reference statements)

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“…Centrosomes are described as microtubule-organising centres (MTOC), acting as dominant sites in spindle assembly (by regulating the formation of spindle poles, which orientates the mitotic bipolar spindle) (Schatten, 2008). Centrosomes are small cytoplasmic organelles made up of a pair of perpendicular centrioles embedded in pericentriolar material.…”

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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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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“…Indeed, a growing number of reports document the recruitment to the centrosomes and the subsequent functional activation of many different proteins, such as cell cycle regulators (e.g., cyclin A and p21 CIP/WAF1 ), kinases (e.g., Aurora A, PLK1, Nek2, PARP1/3, CKIa, CKII), components of the DNA damage response pathways (e.g., BRCA1), proteins regulating apoptosis (e.g., survivin, caspase 3), tumor suppressors (e.g., p53, pRB), transcriptional regulators (e.g., CTCF), and others (reviewed in ref. 16). Thus, Kaiso might also utilize these locations for protein-protein interactions and posttranslational modifications.…”

confidence: 99%

Association of the mammalian transcriptional regulator Kaiso with centrosomes and the midbody

Kantidze¹,

Kamalyukova²,

Razin³

2009

Cell Cycle

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“…The centrosome, which is contributed by the sperm cell, is necessary for the formation of the mitotic spindle [26] and controls the first mitotic divisions post-fertilisation [27]. Centrosomal defects may lead to disorders in fertilisation and early embryonic development [28,29].…”

Section: Discussionmentioning

confidence: 99%

Sperm morphological abnormalities visualised at high magnification predict embryonic development, from fertilisation to the blastocyst stage, in couples undergoing ICSI

Setti

Braga

Vingris

et al. 2014

J Assist Reprod Genet

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Purpose To investigate the predictive value of the motile sperm organelle morphology examination (MSOME) on embryo morphology. Methods The morphologies of 540 embryos obtained from 60 couples undergoing ICSI were evaluated from days 1 to 5 of development and were examined for associations with the percentages of morphologically normal paternal sperm and of the paternal sperm with large nuclear vacuoles (LNVs) as determined by MSOME. Results An increased percentage of LNV sperm was associated with increased odds of a zygote presenting with pronuclear abnormalities. It was also associated with decreased odds of (i) normal cleavage on days 2 and 3 of development, (ii) the presence of a high-quality embryo on day 3, (iii) the development of an embryo to the blastocyst stage, and (iv) an embryo possessing a normal trophectoderm and inner cell mass. The calculated areas under the curves differed for the embryos that did and did not develop to the blastocyst stage and for the high-and low-quality blastocysts. The optimal cut-off value for the percentage of LNV sperm that maximised proper blastocyst formation was ≤24.5 %, and the cut-off value that maximised blastocyst quality was ≤19.5 %.Conclusions These results suggest a very early onset of paternal influences on embryo development. The evaluation of the incidence of vacuoles by MSOME may significantly improve upon the prognostic information provided by conventional semen analyses.

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The mammalian centrosome and its functional significance

Abstract: Primarily known for its role as major microtu-

Cited by 120 publications

References 202 publications

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

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

Association of the mammalian transcriptional regulator Kaiso with centrosomes and the midbody

Sperm morphological abnormalities visualised at high magnification predict embryonic development, from fertilisation to the blastocyst stage, in couples undergoing ICSI

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