The SUMO Pathway in Mitosis

Abstract

Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

Keywords: Condensin; Kinetochore; Mitosis; SUMO; Topoisomerase.

Fig. 10.1

Alternative outcomes of sumoylation. (a) SUMO modification can lead to higher order complex formation. (b) Sumoylation can disrupt protein-protein interaction. (c) SUMO modification can induce conformational alteration, leading to decreased DNA binding affinity. (d) PolySUMO chains can act as a signal for RNF4-mediated ubiquitination and subsequent degradation by the proteasome. SUMO pathway enzymes and ubiquitin pathway enzymes are indicated with “s” and “u” prefix, respectively

Fig. 10.2

Sumoylation targets involved in chromosome condensation and sister chromatid cohesion. Stars indicate subunits of each complex that have been experimentally confirmed as sumoylation targets

Fig. 10.3

Localization of chromosomal sumoylation targets. The distribution of confirmed targets is represented schematically, based upon previously reported localization of the vertebrate homologues. These reported localizations generally reflect the bulk of each vertebrate protein on mitotic chromosomes, not specifically the sumoylated forms. The names of yeast proteins are indicated in boldface type, while vertebrate proteins are in standard type.