Kinetochore–spindle microtubule interactions during mitosis

Abstract

The kinetochore is a proteinaceous structure that assembles onto centromeric DNA and mediates chromosome attachment to microtubules during mitosis. This description is deceivingly simple: recent proteomic studies suggest that the diminutive kinetochores of Saccharomyces cerevisiae are comprised of at least 60 proteins organized into as many as 14 different subcomplexes. Many of these proteins, such as the centromeric histone variant CENP-A, and entire subcomplexes, such as the Ndc80(Hec1) complex, are conserved from yeast to humans despite the diverse nature of the DNA sequences on which they assemble. There have recently been advances in our understanding of the molecular basis of how kinetochores establish dynamic attachments to spindle microtubules, and how these attachments are correctly oriented to ensure segregation of sister chromatids to daughter cells.

New insights into the regulation of anaphase by mitotic cyclins in budding yeast

“…[12][13][14]18,25,26 Once anaphase is initiated, sister chromatids separate and migrate to the pole by the depolymerization of kinetochore microtubules during anaphase A. 10,[12][13][14][15][16][17][18]27 Regrowth of kMTs is inhibited by an as yet ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

“…[8][9][10][11][12][13] The SPB is the microtubule organizing center and organizes three classes of microtubules (MTs). The kinetochore microtubules (kMTs) attach chromosomes via the kinetochore assembled on centromeric DNA sequence during prometaphase and move chromosomes to the SPB; [8][9][10][12][13][14][15][16][17][18][19] the polar microtubules interdigitate in the middle to form the spindle while SPBs undergo separation. 8,10,16,20 Finally, the astral microtubules extend from the SPB into the cytoplasm.…”

The ultrastructure of the kinetochore and kinetochore fiber in Drosophila somatic cells

“…This region contains the four-subunit Ndc80 complex, which has been shown to play a critical role in attaching MTs to kinetochores in a wide range of organisms, including Saccharomyces cerevisiae, Schizosac-charomyces pombe, Caenorhabditis elegans, Xenopus, Gallis gallus, and humans (reviewed by Maiato et al 2004a;DeLuca et al 2005;Kline-Smith et al 2005). On kinetochores that lack MTs, the distal surface of the outer plate appears as a ribosome-free exclusion zone in high-pressure frozen/freeze-substituted specimens, and as a compact fibrous corona in conventionally fixed specimens (McEwen et al 1998).…”

Molecular analysis of mitotic chromosome condensation using a quantitative time-resolved fluorescence microscopy assay

“…Interactions between kinetochores and spindle microtubules play a central role in chromosome alignment and segregation (12,13). Two distinct chromosome architectures are prevalent among metazoans: monocentric, in which kinetochore assembly is restricted to a localized region of each chromatid, and holocentric, in which diffuse kinetochores assemble along the entire chromatid length (14).…”