Chromosome segregation defects

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]. 

Gunderson, C. W. and Segall, A. M. (2006) DNA repair, a novel antibacterial target Holliday junction-trapping peptides induce DNA damage and chromosome segregation defects. Mol. Microbiol. 59, 1129-1148. 

Aneuploidy is consequential to mitotic errors malignantly transformed cells frequently commit mitotic errors. In fetal life, the developing human brain suffers of chromosomal segregational defects during mitoses of glial cells and neurons. Aneuploid brain cells are eliminated by apoptosis. Areas not cleared by apoptosis, remain confined to sites of chromosomal mosaicism. The presence of functionally active aneuploid neurons negatively affect neuron-to-neuron and neuron-to-gUal interactions [1291]. 

Cells with abnormal numbers of chromosomes form when certain cell-cycle checkpoints are nonfunctional. As discussed in Chapter 21, the unreplicated-DNA checkpoint normally prevents entry into mitosis unless all chromosomes have completely replicated their DNA the spindle-assembly checkpoint prevents entry into anaphase unless all the replicated chromosomes attach properly to the metaphase mitotic apparatus and the chromosome-segregation checkpoint prevents exit from mitosis and cytokinesis if the chromosomes segregate improperly (see Figure 21-32, steps [H- 3D. As advances are made in Identifying the proteins that detect these abnormalities and mediate cell-cycle arrest, the molecular basis for the functional defects leading to aneuploidy in tumor cells will become clearer. 

Identification of mutants defective in meiotic recombination have been particularly informative about meiosis analysis of such mutants has revealed that genetic recombination is essential for proper chromosome segregation (reviewed in Hawley, 1987). Several mutant screens have been developed that look for mutants... 

Paclitaxel belongs to the family of cytoskeletal drugs which target tubulin. Treatment leads to abnormality of the mitotic spindle assembly, chromosome segregation, and consequently defects of cell division. By stabilizing the microtubule polymer and preventing the disassembly of microtubules, paclitaxel arrests cell cycle in the GO/Gl and G2/M phases and induces apoptosis [134]. 

Petite mutants spontaneous mutants, chiefly yeasts, with chemical or physical defects in the respiratory chain. P. m. grow very slowly and form small ( petite ) colonies on nutrient agar. The same phenotype can be produced by a chromosomal mutation (segregational petite), or a mutation in the mitochondrial DNA (vegetative or neutral petite). In the latter case, mitochondrial structure is considerably altered, largely due to changes in the amino acid composition of the structural proteins of the inner mitochondrial membrane. Since these structural proteins are important for the correct arrangement and conformation of the respiratory chain enzymes, the effect of petite mutation on the respiratory chain is probably secondary. 

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