Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle

Spremo-Potparević, Biljana; Živković, Lada; Djelić, Ninoslav; Bajić, Vladan

doi:10.1016/j.exger.2004.01.012

Cited by 33 publications

(42 citation statements)

References 26 publications

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“…It involves not only the centromere but also the entire sister chromatids of almost all mitotic chromosomes in a given metaphase [Kajii and Ikeuchi, 2004]. PSCS has been described in a number of conditions including Roberts syndrome [German, 1979], Fanconi Anemia, Ataxia Teleangiectasia [Mehes and Buhler, 1995], Alzheimer disease [Moorhead and Heyman, 1983;Spremo-Potparevic et al, 2004], Tuberous Sclerosis [Scappaticci et al, 1988], and Variegated Aneuploidy [Kajii et al, 1998;Plaja et al, 2001Plaja et al, , 2003. Recently, mutations in the BUB1B gene were found to be a cause of multiple variegated aneuploidy [Hanks et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome

et al. 2005

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The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited multisystem developmental disorder. The phenotype consists of characteristic facial features, hirsutism, abnormalities of the upper extremities ranging from subtle changes in the phalanges and metacarpal bones to oligodactyly and phocomelia, gastroesophageal dysfunction, growth retardation, and neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000. Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases. To date, mutations in this gene have been identified in over 45% of individuals with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although its function in mammalian systems has not yet been elucidated, sequence homologs of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion during mitosis, and a similar role was recently demonstrated for Nipped-B in Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL mutation negative) with CdLS were evaluated for evidence of precocious sister chromatid separation (PSCS). We screened 50 metaphases from each proband and found evidence of PSCS in 41% (compared to 9% in control samples). These studies indicate that NIPBL may play a role in sister chromatid cohesion in humans as has been reported for its homologs in Drosophila and yeast.

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Section: Discussionmentioning

confidence: 99%

Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome

et al. 2005

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“…Research has shown that PCS appears considerably earlier than previously presumed, i.e., in the interphase of the cell cycle [30,32]. The fluorescent in situ hybridization (FISH) method applied to the centromere region of the X chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients demonstrated that PCS appears considerably before mitotic metaphase, directly after completion of DNA replication in G 2 phase of the cell cycle [30][31][32].…”

Section: Chromosomes and The Fourth Dimensional Control Of The Cell Cmentioning

confidence: 99%

“…The fluorescent in situ hybridization (FISH) method applied to the centromere region of the X chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients demonstrated that PCS appears considerably before mitotic metaphase, directly after completion of DNA replication in G 2 phase of the cell cycle [30][31][32]. Using FISH, an analysis of PCS of the X chromosomes was made of histopatologic slides of neurons from the frontal cerebral cortex, in a group of sporadic AD patients and in age-matched controls [50].…”

Section: Chromosomes and The Fourth Dimensional Control Of The Cell Cmentioning

confidence: 99%

“…How serious changes in time regulation can be is perhaps best exemplified by primary repeated non-disjunction of chromosome 21, X and 18 by PCS in women clinically normal and who have Down offspring having twice the chance to develop AD [47][48][49]. Notably, there is a preferential susceptibility of chromosomes X, 18 and 21 to aneuploidy in aged and AD subjects [30,32,38,[42][43][44]46,50].…”

Section: Chromosomes and The Fourth Dimensional Control Of The Cell Cmentioning

confidence: 99%

“…Using a scientific approach quite different from approaches used to date, work done on the alterations of centromere dynamics in interphase nuclei of neuronal cells and peripheral blood lymphocytes of AD patients [30][31][32] have confirmed not only that these cells undergo mitosis but that the temporal dynamics of centromeres are highly altered.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?

Bajić

Spremo-Potparević

Živković

et al. 2008

Bioscience Hypotheses

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Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase-anaphase transition separate in a non-random, sequential order. This sequence has been shown to be deregulated in aging cells, various tumors, syndromes of chromosome instability, following certain chemical inductions, as well as in AD. Over time, premature chromosome separation is both a result of, and a driving force behind, further cohesion impairment, activation of cyclin dependent kinases, and mitotic catastrophe, a vicious circle resulting in cellular degeneration and death.

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Effect of chain modifications on the physicomechanical properties of silsesquioxane‐based dental nanocomposites

2007

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The objective of this study was to evaluate the physicomechanical properties of a series of polyhedral silsesquioxane (SSQ) methacrylate monomers developed for dental applications. The effect of chain modifications on the properties of the SSQ-based monomers was also evaluated. Physicomechanical properties that are investigated include polymerization shrinkage, degree of conversion, hardness, and modulus. Results obtained were compared with unfilled 1:1 (control) bis-GMA/TEGDMA materials (typical monomers used in dental composites). All samples investigated were cured using 400-500 nm light at 500 mW/cm(2) for 40 s. Shrinkage associated with curing and post-gel reactions for all synthesized SSQ compounds were found to range from (0.04 +/- 0.01)% to (0.33 +/- 0.03)% with degree of conversion ranging from (56.68 +/- 2.81)% to (84.53 +/- 2.62)%. At all time intervals, post-gel shrinkage associated with control was found to be significantly greater than all SSQ compounds. No significant difference in degree of conversion was observed for control, and all SSQ compounds except for SSQ attached with eight equivalents of short-chain methacrylate. Mechanical properties associated with SSQ compounds were found to be significantly lower than control. However, through chain modifications, mechanical properties of SSQ compounds can be improved by approximately 50%.

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Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle

Cited by 33 publications

References 26 publications

Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome

Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome

Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?

Effect of chain modifications on the physicomechanical properties of silsesquioxane‐based dental nanocomposites

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