Holding Your Own: Establishing Sister Chromatid Cohesion
- Dept. of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA
This extract was created in the absence of an abstract.
Chromosome Segregation and Genome Integrity
At cell division, both daughter cells receive only one copy of the parental genome. Not surprisingly, chromatin plays a role at numerous stages to ensure that genome segregation occurs with high fidelity. First, each chromosome is duplicated to produce two identical chromosomes called sister chromatids. Second, sister chromatids become paired, or glued together, along the entire chromosome length (Sumner 1991; Selig et al. 1992; Guacci et al. 1994). This pairing, or cohesion, provides a mechanism by which the identity of sister chromatids can be maintained over time. Third, sister pairs associate with the mitotic spindle apparatus via kinetochores, specialized protein complexes that assemble on centromeres. This association produces a highly defined geometry: The kinetochore of one chromatid associates with microtubules from the spindle pole opposite that of her sister. Cohesion between sister chromatids facilitates this orientation, most probably by physically constraining sister kinetochores to face in opposite directions (Rieder 1982; Waters et al. 1996; Michaelis et al. 1997; Tanaka et al. 2000a). Fourth, kinetochores associated with spindle microtubules generate poleward-pulling forces that act to separate sister chromatids (McNeill and Berns 1981; Rieder et al. 1986; Skibbens et al. 1995). Cohesion opposes these kinetochore pulling forces, stretching the intervening chromatin and generating tension across the chromatid pair. This tension is critical for coordinating sister chromatid movement during mitosis (Skibbens et al. 1995), and for cell cycle progression. In support of the latter, kinetochores capture microtubules by chance, such that initial attachments are not always correct (Nicklas 1997). Fortunately, cells have evolved a mitotic checkpoint mechanism that halts cell cycle progression in response to inappropriate kinetochore–microtubule interactions or in the absence of tension (Hoyt et al. 1991; Li and Murray 1991; Nicklas et al. 1995; Li and Nicklas 1997; Waters et …
