Drosophila Aurora B Kinase Is Required for Histone H3 Phosphorylation and Condensin Recruitment during Chromosome Condensation and to Organize the Central Spindle during Cytokinesis

By R. Giet, David Glover. Journal of Cell Biology, 2001

667 citations recorded by the source corpus.

Aurora/Ipl1-related kinases are a conserved family of enzymes that have multiple functions during mitotic progression. Although it has been possible to use conventional genetic analysis to dissect the function of aurora, the founding family member in Drosophila (Glover, D.M., M.H. Leibowitz, D.A. McLean, and H. Parry. 1995. Cell. 81:95–105), the lack of mutations in a second aurora-like kinase gene, aurora B, precluded this approach. We now show that depleting Aurora B kinase using double-stranded RNA interference in cultured Drosophila cells results in polyploidy. aurora B encodes a passenger protein that associates first with condensing chromatin, concentrates at centromeres, and then relocates onto the central spindle at anaphase. Cells depleted of the Aurora B kinase show only partial chromosome condensation at mitosis. This is associated with a reduction in levels of the serine 10 phosphorylated form of histone H3 and a failure to recruit the Barren condensin protein onto chromosomes. These defects are associated with abnormal segregation resulting from lagging chromatids and extensive chromatin bridging at anaphase, similar to the phenotype of barren mutants (Bhat, M.A., A.V. Philp, D.M. Glover, and H.J. Bellen. 1996. Cell. 87:1103–1114.). The majority of treated cells also fail to undertake cytokinesis and show a reduced density of microtubules in the central region of the spindle. This is accompanied by a failure to correctly localize the Pavarotti kinesin-like protein, essential for this process. We discuss these conserved functions of Aurora B kinase in chromosome transmission and cytokinesis.

Subfields: Cell Biology, Plant Science

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Citations in the corpus

• The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint (2003, background): “Aurora B appears to be required for several mitotic processes, including chromosome congression to the spindle equator, chromosome segregation, and cytokinesis (Kaitna et al., 2000; Adams et al., 2001b; Giet and Glover, 2001; Kaitna et al., 2002; Kallio et al., 2002; Murata-Hori and Wang, 2002; Mura”
• Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. (2004, background): “The action of these particular kinases is thought to be required for the proper recruitment of the condensin complex and assembly of the mitotic spindle in a phosphorylated histone H3-dependent manner [ 22 ].”
• Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “Mitotic H3S10 phosphorylation is mainly controlled by Aurora B (Adams et al., 2001; Giet and Glover, 2001; Richie and Golden, 2005), Aurora A (Kim et al., 2016), and polo-like kinase 1 (PLK1).”
• Mitotic Phosphorylation of Histone H3: Spatio-Temporal Regulation by Mammalian Aurora Kinases (2002, background): “It first appears in the G2/M phase, initiating at pericentromeric heterochromatin, and then progresses along the chromosomal arms until it spreads to the whole chromosome (15, 23, 26).”
• Roles of Aurora Kinases in Mitosis and Tumorigenesis (2007, background): “elegans embryos and Drosophila S2 cells (4, 66).”
• Aurora-kinase inhibitors as anticancer agents (2004, background): “Although it is not yet clear which Aurora kinase is inhibited to mediate the antitumour effects of these drugs, Aurora-B is probably the primary target, as inhibition of this kinase, by any method, results in a catastrophic mitosi”
• Functional diversity of protein phosphatase-1, a cellular economizer and reset button. (2004, background): “Various studies have reported a correlation between the phosphorylation of histone H3 along chromosomes in G2 and chromosome condensation (146, 176, 375), and also between chromosome decondensation in telophase and PP1 activity or histone H3 dephosphorylation (24, 151, 368).”