Chromokinesins

Abstract

During the cell cycle it is critical that the duplicated DNA faithfully segregates to give rise to two genetically identical daughter cells. An even distribution of the genome during mitosis is mediated by mitotic spindle microtubules, assisted by, among others, motor proteins of the kinesin superfamily. Chromokinesins are members of the kinesin superfamily that harbour a specific DNA-binding domain. The best characterized chromokinesins belong to the kinesin-4/Kif4 and kinesin-10/Kif22 families, respectively. Functional analysis of chromokinesins in several model systems revealed their involvement in chromosome arm orientation and oscillations. This is consistent with their originally proposed role in the generation of polar ejection forces that assist chromosome congression to the spindle equator. Kinesin-12/Kif15 members comprise a third family of chromokinesins, but their role remains less understood. Noteworthy, all chromokinesins exhibit chromosome-independent localization on spindle microtubules, and recent works have significantly extended the portfolio of mitotic processes in which chromokinesins play a role, from error correction and DNA compaction, to the regulation of spindle microtubule dynamics.

Figure 1. The Chromokinesin Family.

(A) Phylogenetic tree of all Chromokinesins expressed in humans (Hs), mouse (Mm), Chicken (Gg), Xenopus (Xl), D. melanogaster (Dm) and C. elegans (Ce). (B) Schematic representation of the three human Chromokinesins. All Chromokinesins share a conserved N-terminal motor domain (blue), followed by a stalk consisting of coiled-coil regions of different lengths (white). Nuclear localization signals (NLS) in Kif4a and Kid are indicated in dashed lines in the stalk. The chromosome binding domains are represented in green boxes: a zip/basic/leucine zip (ZBZ) domain and a Cystein-Rich (C-R) motif for kinesin-4; an Helix-hairpin-Helix (HhH) motif for kinesin-10 and a region that interacts with the protein Ki67 for kinesin-12. aa, amino acids.

Figure 2. Mitotic roles of kinesin-10 and kinesin-4.

(A) Female Indian muntjac fibroblast depleted of Kid/kinesin-10 by RNAi. Arrows indicate chromosome armorientation problems suggesting a role in PEFs. (B) Female Indian muntjac fibroblast depleted of Kif4a/kinesin-4 by RNAi. Arrow indicate a lagging chromosome during anaphase suggesting a role in error-correction and chromosome segregation fidelity. Time is in h:min. Scale bars = 5 μm.