Basic mechanism of eukaryotic chromosome segregation

Abstract

We now have firm evidence that the basic mechanism of chromosome segregation is similar among diverse eukaryotes as the same genes are employed. Even in prokaryotes, the very basic feature of chromosome segregation has similarities to that of eukaryotes. Many aspects of chromosome segregation are closely related to a cell cycle control that includes stage-specific protein modification and proteolysis. Destruction of mitotic cyclin and securin leads to mitotic exit and separase activation, respectively. Key players in chromosome segregation are SMC-containing cohesin and condensin, DNA topoisomerase II, APC/C ubiquitin ligase, securin-separase complex, aurora passengers, and kinetochore microtubule destabilizers or regulators. In addition, the formation of mitotic kinetochore and spindle apparatus is absolutely essential. The roles of principal players in basic chromosome segregation are discussed: most players have interphase as well as mitotic functions. A view on how the centromere/kinetochore is formed is described.

Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe

“…Caffeine likewise induced premature entry into mitosis when the topoisomerase-II toxin Adriamycin (ADR) was used as a genotoxic agent (Figure 1c). APC/C substrates remained stabilized and cells continued to display a 4N DNA content after the ADR-caffeine treatment (Figure 1d), probably because topoisomerase-II activity is required for chromosome segregation (Yanagida, 2005).…”

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

“…In recent years, many of the proteins that mediate sister chromatid cohesion and its dissolution have been discovered and characterized. There are recent reviews that cover the structure and function of the sister chromatid cohesion apparatus in chromosome segregation (Nasmyth 2005;Nasmyth and Haering 2005;Yanagida 2005;Huang et al 2005;Hirano 2005), and on its potential roles in Cornelia de Lange syndrome (Dorsett 2004;Strachan 2005). In this paper, I review certain key components of the cohesion apparatus, discuss their roles in gene expression and development in model organisms, and then the implications of the model organism studies for Cornelia de Lange and Roberts-SC phocomelia human genetic syndromes.…”

The Role of Model Organisms in the History of Mitosis Research

“…All cut-like mutants turned out to be defective in important mitotic steps, such as chromosome condensation, segregation, activation of separase, control of ubiquitin-mediated proteolysis, spindle formation, spindle elongation, cytokinesis, etc. (Yanagida 2005). Among them, mutants in top2, separase cut1, and condensin cut3 produced highly similar phenotypes.…”

“…Systematic screening of fission yeast mitotic mutants (ts and cold-sensitive [cs]) was performed. A number of genes were identified and their products were characterized (reviewed in Yanagida 2005). Three principal chromosome segregation defects (arrest, cut, and unequal) were found for this organism at the restrictive temperature (Fig.…”