Chromosome segregation

The activated CDKl-cyclin B kinase finally phosphor-ylates a large number of proteins most of which are not well characterized, leading to chromosome condensation, nuclear envelope breakdown, spindle assembly, and chromosome segregation. 

Chromosomal Translocations Chromosome Segregation Chromosomes Chronic Bronchitis... 

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Murray AW, Szostak TW 1985 Chromosome segregation in mitosis and meiosis. Annu Rev Cell Biol 1 289-315... 

Ramel C. 1973. The effect of metal compounds on chromosome segregation. Mut Res 21 45-46. 

Crebelli, R., Andreoli, C., Carere, A., Conti, L., Crochi, B., Cotta-Ramusino, M., Benigni, R. Toxicology of halogenated aliphatic hydrocarbons Structural and molecular determinants for the disturbance of chromosome segregation and the induction of lipid peroxidation. Chem. Biol. Interact. 1995, 98, 113-129. 

Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome ahgnment, kinetochore disjunction, chromosome segregation. J Cell Biol 153(4) 865-880 Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Alhs CD (2005a) Sterile 20 kinase phospho-rylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120(l) 25-36... 

Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M (2002) Increased mitotic phosphorylation of histone H3 attributable to AIM-l/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 62(18) 5168-5177 Paulson JR, Taylor SS (1982) Phosphorylation of histones 1 and 3 and nonhistone high mobihty group 14 by an endogenous kinase in HeLa metaphase chromosomes. J Biol Chem 257(11) 6064—6072 Petersen J, Paris J, Wilier M, Philippe M, Hagan IM (2001) The S. pombe aurora-related kinase Arkl associates with mitotic structures in a stage dependent manner and is required for chromosome segregation. J Cell Sci 114(Pt 24) 4371 384... 

One unresolved question is whether CENP-A effects the stability of centromeric chromatin. One interesting possibility is that CENP-A promotes an unusually stable chromatin structure that is adapted to withstanding the forces exerted on the centromere during chromosome segregation [23]. Reconstitution of nucleosome arrays with CENP-A may provide insights into this question. 

The gene that encodes H2A.Z is essential in Drosophila [42], Tetrahymena [43], and mice [44]. Deletion of the gene that encodes H2A.Z in yeast results in slow growth and chromosome segregation defects in Schizosaccharomyces pompe [38], and in slow growth and defects in gene regulation in Saccharomyces cerevisiae [45-48]. 

Studies over the last 10 years clearly demonstrate the importance of histone variants in modifying nucleosome structure and function. They play specialized roles in diverse chromatin functions including transcriptional regulation, DNA repair, chromosome segregation, spermatogenesis, and histone replacement. 

Hsu, J.M., Huang, J., Meluh, P.B., and Laurent, B.C. (2003) The yeast RSC chromatin-remodeling complex is required for kinetochore function in chromosome segregation. Mol. Cell. Biol. 23, 3202-3215. 

Yoo, E.J., Jin, Y.H., Jang, Y.K., Bjerling, P., Tabish, M., Hong, S.H., Ekwall, K., and Park, S.D. (2000) Fission yeast hrpl, a chromodomain ATPase, is required for proper chromosome segregation and its overexpression interferes with chromatin condensation. Nucleic Acids Res. 28, 2004-2011. 

The vinca alkaloids comprise vincristine and vinblastine. These complex, heterocyclic alkaloids are derived from the periwinkle plant. Vindesine and vi-norelbine are semisynthetic analogues. These drugs are M-phase specitic. Binding specifically to tubulin they inhibit the polymerization of microtubules. The consequent ineffective chromosome segregation initiates apoptosis for both normal and malignant cells. 

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