scholarly journals Aurora B Regulates Formin mDia3 in Achieving Metaphase Chromosome Alignment

2011 ◽  
Vol 20 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Lina Cheng ◽  
Jiayin Zhang ◽  
Sana Ahmad ◽  
Lorene Rozier ◽  
Haiqian Yu ◽  
...  
Keyword(s):  
Metaphase Chromosome ◽  
Aurora B ◽  
Chromosome Alignment

scholarly journals Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation

2012 ◽  
Vol 199 (2) ◽  
pp. 251-268 ◽  
Author(s):  
Fangwei Wang ◽  
Natalia P. Ulyanova ◽  
John R. Daum ◽  
Debasis Patnaik ◽  
Anna V. Kateneva ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Metaphase Chromosome ◽  
Histone H3 ◽  
Spindle Checkpoint ◽  
Aurora B ◽  
Docking Site ◽  
Chromosome Movement ◽  
Checkpoint Signaling ◽  
Chromosome Alignment ◽  
Spindle Midzone

Haspin phosphorylates histone H3 at threonine-3 (H3T3ph), providing a docking site for the Aurora B complex at centromeres. Aurora B functions to correct improper kinetochore–microtubule attachments and alert the spindle checkpoint to the presence of misaligned chromosomes. We show that Haspin inhibitors decreased H3T3ph, resulting in loss of centromeric Aurora B and reduced phosphorylation of centromere and kinetochore Aurora B substrates. Consequently, metaphase chromosome alignment and spindle checkpoint signaling were compromised. These effects were phenocopied by microinjection of anti-H3T3ph antibodies. Retargeting Aurora B to centromeres partially restored checkpoint signaling and Aurora B–dependent phosphorylation at centromeres and kinetochores, bypassing the need for Haspin activity. Haspin inhibitors did not obviously affect phosphorylation of histone H3 at serine-10 (H3S10ph) by Aurora B on chromosome arms but, in Aurora B reactivation assays, recovery of H3S10ph was delayed. Haspin inhibitors did not block Aurora B localization to the spindle midzone in anaphase or Aurora B function in cytokinesis. Thus, Haspin inhibitors reveal centromeric roles of Aurora B in chromosome movement and spindle checkpoint signaling.

scholarly journals Essential Roles of Drosophila Inner Centromere Protein (Incenp) and Aurora B in Histone H3 Phosphorylation, Metaphase Chromosome Alignment, Kinetochore Disjunction, and Chromosome Segregation

2001 ◽  
Vol 153 (4) ◽  
pp. 865-880 ◽  
Author(s):  
Richard R. Adams ◽  
Helder Maiato ◽  
William C. Earnshaw ◽  
Mar Carmena
Keyword(s):  
Metaphase Chromosome ◽  
Cultured Cells ◽  
Histone H3 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Centromere Protein ◽  
H3 Phosphorylation ◽  
Chromosome Alignment ◽  
Chromosomal Passenger Proteins

We have performed a biochemical and double-stranded RNA-mediated interference (RNAi) analysis of the role of two chromosomal passenger proteins, inner centromere protein (INCENP) and aurora B kinase, in cultured cells of Drosophila melanogaster. INCENP and aurora B function is tightly interlinked. The two proteins bind to each other in vitro, and DmINCENP is required for DmAurora B to localize properly in mitosis and function as a histone H3 kinase. DmAurora B is required for DmINCENP accumulation at centromeres and transfer to the spindle at anaphase. RNAi for either protein dramatically inhibited the ability of cells to achieve a normal metaphase chromosome alignment. Cells were not blocked in mitosis, however, and entered an aberrant anaphase characterized by defects in sister kinetochore disjunction and the presence of large amounts of amorphous lagging chromatin. Anaphase A chromosome movement appeared to be normal, however cytokinesis often failed. DmINCENP and DmAurora B are not required for the correct localization of the kinesin-like protein Pavarotti (ZEN-4/CHO1/MKLP1) to the midbody at telophase. These experiments reveal that INCENP is required for aurora B kinase function and confirm that the chromosomal passengers have essential roles in mitosis.

scholarly journals Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast

2011 ◽  
Vol 22 (9) ◽  
pp. 1473-1485 ◽  
Author(s):  
Zuzana Storchová ◽  
Justin S. Becker ◽  
Nicolas Talarek ◽  
Sandra Kögelsberger ◽  
David Pellman
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Spindle Pole ◽  
Growth Defect ◽  
Aurora B ◽  
Mitotic Kinase ◽  
Sister Chromatids ◽  
Chromosome Alignment ◽  
Chromosomal Passenger

The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B–independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B–mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments.

scholarly journals BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment

2007 ◽  
Vol 179 (2) ◽  
pp. 357-357
Author(s):  
Jiayin Zhang ◽  
Sana Ahmad ◽  
Yinghui Mao
Keyword(s):  
Metaphase Chromosome ◽  
Chromosome Alignment

scholarly journals Elevated polar ejection forces stabilize kinetochore–microtubule attachments

2013 ◽  
Vol 200 (2) ◽  
pp. 203-218 ◽  
Author(s):  
Stuart Cane ◽  
Anna A. Ye ◽  
Sasha J. Luks-Morgan ◽  
Thomas J. Maresca
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Critical Force ◽  
Aurora B ◽  
Dependent Manner ◽  
Spindle Poles ◽  
Ejection Force ◽  
Chromosome Alignment ◽  
Directed Motility ◽  
Spindle Microtubules

Chromosome biorientation promotes congression and generates tension that stabilizes kinetochore–microtubule (kt-MT) interactions. Forces produced by molecular motors also contribute to chromosome alignment, but their impact on kt-MT attachment stability is unclear. A critical force that acts on chromosomes is the kinesin-10–dependent polar ejection force (PEF). PEFs are proposed to facilitate congression by pushing chromosomes away from spindle poles, although knowledge of the molecular mechanisms underpinning PEF generation is incomplete. Here, we describe a live-cell PEF assay in which tension was applied to chromosomes by manipulating levels of the chromokinesin NOD (no distributive disjunction; Drosophila melanogaster kinesin-10). NOD stabilized syntelic kt-MT attachments in a dose- and motor-dependent manner by overwhelming the ability of Aurora B to mediate error correction. NOD-coated chromatin stretched away from the pole via lateral and end-on interactions with microtubules, and NOD chimeras with either plus end–directed motility or tip-tracking activity produced PEFs. Thus, kt-MT attachment stability is modulated by PEFs, which can be generated by distinct force-producing interactions between chromosomes and dynamic spindle microtubules.

scholarly journals Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1

2019 ◽  
Vol 218 (4) ◽  
pp. 1235-1249 ◽  
Author(s):  
Thomas E. Bass ◽  
David Cortez
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Kinase Activity ◽  
Aurora B ◽  
Gene Ontology Analysis ◽  
Quantitative Mass Spectrometry ◽  
Checkpoint Response ◽  
Damage Response ◽  
Chromosome Alignment ◽  
Atr Kinase ◽  
Atr Activation

The ATR kinase controls cell cycle transitions and the DNA damage response. ATR activity is regulated through two ATR-activating proteins, ETAA1 and TOPBP1. To examine how each activator contributes to ATR signaling, we used quantitative mass spectrometry to identify changes in protein phosphorylation in ETAA1- or TOPBP1-deficient cells. We identified 724, 285, and 118 phosphosites to be regulated by TOPBP1, ETAA1, or both ATR activators, respectively. Gene ontology analysis of TOPBP1- and ETAA1-dependent phosphoproteins revealed TOPBP1 to be a primary ATR activator for replication stress, while ETAA1 regulates mitotic ATR signaling. Inactivation of ATR or ETAA1, but not TOPBP1, results in decreased Aurora B kinase activity during mitosis. Additionally, ATR activation by ETAA1 is required for proper chromosome alignment during metaphase and for a fully functional spindle assembly checkpoint response. Thus, we conclude that ETAA1 and TOPBP1 regulate distinct aspects of ATR signaling with ETAA1 having a dominant function in mitotic cells.

Sign in / Sign up

Export Citation Format

Share Document