Spindle Checkpoint - Sister Chromatids Cohesion During Mitosis - Function of Cohesion and Its Dissolution

Function of Cohesion and Its Dissolution

Centromeric cohesion resists the forces exerted by spindle microtubules towards the poles, which generate tension between sister kinetochores. In turn, this tension stabilizes the attachment microtubule-kinetochore, through a mechanism implicating the protein Aurora B (a review about this issue : Hauf and Watanabe 2004).

Indeed, a decrease in the cellular levels of cohesin generates the premature separation of sister chromatids, as well as defects in chromosome congression at the metaphase plate and delocalization of the proteins in the chromosomal passenger complex, which contains the protein Aurora B. The proposed structure for the cohesin complex suggests that this complex connects directly both sister chromatids. In this proposed structure, the SMC components of cohesin play a structural role, so that the SMC heterodimer may function as a DNA binding protein, whose conformation is regulated by ATP. Scc1p and Scc3p, however, would play a regulatory role.

In S. cerevisiae, Pds1p (also known as securin) regulates sister chromatids cohesion, because it binds and inhibits the protease Esp1p (separin or separase). When anaphase onset is triggered, the anaphase-promoting complex (APC/C or Cyclosome) degrades securin. Securin degradation releases the protease Esp1p/separase, which degrades the cohesin rings that link the two sister chromatids, therefore promoting sister chromatids separation. It has been also shown that Polo/Cdc5 kinase phosphorylates serine residues next to the cutting site for Scc1, and this phosphorylation would facilitate the cutting activity.

Although this machinery is conserved through evolution, in vertebrates most cohesin molecules are released in prophase, independently of the presence of the APC/C, in a process dependent on Polo-like 1 (PLK1) and Aurora B. Yet it has been shown that a small quantity of Scc1 remains associated to centromeres in human cells until metaphase, and a similar amount is cut in anaphase, when it disappears from centromeres. On the other hand, some experiments show that sister chromatids cohesion in the arms is lost gradually after sister centromeres have separated, and sister chromatids move toward the opposite poles of the cell.

According to some observations, a fraction of cohesins in the chromosomal arms and the centromeric cohesins are protected by the protein Shugoshin (Sgo1), avoiding their release during prophase. To be able to function as protector for the centromeric cohesion, Sgo1 must be inactivated at the beginning of anaphase, as well as Pds1p. In fact, both Pds1p and Sgo1 are substrates of APC/C in vertebrates.

Read more about this topic:  Spindle Checkpoint, Sister Chromatids Cohesion During Mitosis

Famous quotes containing the words function of, dissolution, function and/or cohesion:

    Advocating the mere tolerance of difference between women is the grossest reformism. It is a total denial of the creative function of difference in our lives. Difference must be not merely tolerated, but seen as a fund of necessary polarities between which our creativity can spark like a dialectic.
    Audre Lorde (1934–1992)

    ...that absolutely everything beloved and cherished of the bourgeoisie, the conservative, the cowardly, and the impotent—the State, family life, secular art and science—was consciously or unconsciously hostile to the religious idea, to the Church, whose innate tendency and permanent aim was the dissolution of all existing worldly orders, and the reconstitution of society after the model of the ideal, the communistic City of God.
    Thomas Mann (1875–1955)

    The press and politicians. A delicate relationship. Too close, and danger ensues. Too far apart and democracy itself cannot function without the essential exchange of information. Creative leaks, a discreet lunch, interchange in the Lobby, the art of the unattributable telephone call, late at night.
    Howard Brenton (b. 1942)

    The birth of the new constitutes a crisis, and its mastery calls for a crude and simple cast of mind—the mind of a fighter—in which the virtues of tribal cohesion and fierceness and infantile credulity and malleability are paramount. Thus every new beginning recapitulates in some degree man’s first beginning.
    Eric Hoffer (1902–1983)