|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 110, Issue 5 537-545, Copyright © 1997 by Company of Biologists
JOURNAL ARTICLES |
X Li and RB Nicklas
Department of Zoology, Duke University, Durham, NC 27708-1000, USA.
Improper chromosome attachment to the spindle can lead to daughter cells with missing or extra chromosomes. Such mishaps are avoided in many cells by a checkpoint that detects even a single improperly attached chromosome. What is detected? A misattached chromosome is not under tension from opposed mitotic forces, and in praying mantid spermatocytes, direct experiments show that the absence of tension is what the checkpoint detects. How is the absence of tension detected? Tension-sensitive kinetochore protein phosphorylation is the most likely possibility. We combined micromanipulation with immunostaining for phosphoproteins in order to study the effect of tension on kinetochore phosphorylation in mantid spermatocytes. We confirm earlier observations on mammalian cells and grasshopper spermatocytes that misattached chromosomes have phosphorylated kinetochore proteins. We also confirm experiments in grasshopper spermatocytes showing that tension alters kinetochore chemistry: tension from a micromanipulation needle causes kinetochore protein dephosphorylation, and relaxation of tension causes kinetochore protein rephosphorylation. Beyond confirmation, our results provide fresh evidence for phosphorylation as the signal to the checkpoint. First, mantid cells are the only ones in which an effect of tension on the checkpoint has been directly demonstrated; by equally direct experiments, we now show that tension affects kinetochore phosphorylation in these same cells. Second, sex chromosome behavior in mantids provides a natural experiment to test the relationship between phosphorylation and the checkpoint. In grasshoppers, an unpaired sex chromosome is normal, its kinetochore is under-phosphorylated, and the checkpoint is not activated. In mantids, exactly the opposite is true: an unpaired sex chromosome is abnormal, its kinetochore is phosphorylated and, as predicted, the checkpoint is activated. We conclude that tension-sensitive kinetochore protein phosphorylation very likely is the essential link between proper chromosome attachment and the check-point, the link that permits potential errors in chromosome distribution to be detected and avoided.
This article has been cited by other articles:
|
|
 |
|
  Y. Lou, J. Yao, A. Zereshki, Z. Dou, K. Ahmed, H. Wang, J. Hu, Y. Wang, and X. Yao NEK2A Interacts with MAD1 and Possibly Functions as a Novel Integrator of the Spindle Checkpoint Signaling J. Biol. Chem., May 7, 2004; 279(19): 20049 - 20057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Logarinho, H. Bousbaa, J. M. Dias, C. Lopes, I. Amorim, A. Antunes-Martins, and C. E. Sunkel Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cells J. Cell Sci., May 1, 2004; 117(9): 1757 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Douglas and G. G. Haddad Genetic Models in Applied Physiology: Invited Review: Effect of oxygen deprivation on cell cycle activity: a profile of delay and arrest J Appl Physiol, May 1, 2003; 94(5): 2068 - 2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Wilson, A. Forer, and D. Wise Microtubule distribution during meiosis I in flea-beetle [Alagoasa (Oedionychus)] spermatocytes: evidence for direct connections between unpaired sex chromosomes J. Cell Sci., April 1, 2003; 116(7): 1235 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-T. Liu, G. K.T. Chan, J. C. Hittle, G. Fujii, E. Lees, and T. J. Yen Human MPS1 Kinase Is Required for Mitotic Arrest Induced by the Loss of CENP-E from Kinetochores Mol. Biol. Cell, April 1, 2003; 14(4): 1638 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, J. Yao, and H. C. Joshi Attachment and tension in the spindle assembly checkpoint J. Cell Sci., September 15, 2002; 115(18): 3547 - 3555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Garber and J. Rine Overlapping Roles of the Spindle Assembly and DNA Damage Checkpoints in the Cell-Cycle Response to Altered Chromosomes in Saccharomyces cerevisiae Genetics, June 1, 2002; 161(2): 521 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Eaker, A. Pyle, J. Cobb, and M. A. Handel Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice J. Cell Sci., March 10, 2002; 114(16): 2953 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cimini, D. Fioravanti, E. D. Salmon, and F. Degrassi Merotelic kinetochore orientation versus chromosome mono-orientation in the origin of lagging chromosomes in human primary cells J. Cell Sci., January 2, 2002; 115(3): 507 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Skibbens Holding Your Own: Establishing Sister Chromatid Cohesion Genome Res., November 1, 2000; 10(11): 1664 - 1671. [Full Text]
|
|
|
|
 |
|
 H.-G. Yu and R. K. Dawe Functional Redundancy in the Maize Meiotic Kinetochore J. Cell Biol., October 3, 2000; 151(1): 131 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-G. Yu, M. G. Muszynski, and R. Kelly Dawe The Maize Homologue of the Cell Cycle Checkpoint Protein MAD2 Reveals Kinetochore Substructure and Contrasting Mitotic and Meiotic Localization Patterns J. Cell Biol., May 3, 1999; 145(3): 425 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Daum and G. J. Gorbsky Casein Kinase II Catalyzes a Mitotic Phosphorylation on Threonine 1342 of Human DNA Topoisomerase IIalpha , Which Is Recognized by the 3F3/2 Phosphoepitope Antibody J. Biol. Chem., November 13, 1998; 273(46): 30622 - 30629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.K.T. Chan, B.T. Schaar, and T.J. Yen Characterization of the Kinetochore Binding Domain of CENP-E Reveals Interactions with the Kinetochore Proteins CENP-F and hBUBR1 J. Cell Biol., October 5, 1998; 143(1): 49 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Maney, A. W. Hunter, M. Wagenbach, and L. Wordeman Mitotic Centromere-associated Kinesin Is Important for Anaphase Chromosome Segregation J. Cell Biol., August 10, 1998; 142(3): 787 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Taylor, E. Ha, and F. McKeon The Human Homologue of Bub3 Is Required for Kinetochore Localization of Bub1 and a Mad3/Bub1-related Protein Kinase J. Cell Biol., July 13, 1998; 142(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gorbsky, R.-H. Chen, and A. W. Murray Microinjection of Antibody to Mad2 Protein into Mammalian Cells in Mitosis Induces Premature Anaphase J. Cell Biol., June 1, 1998; 141(5): 1193 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nicklas, M. Campbell, S. Ward, and G. Gorbsky Tension-sensitive kinetochore phosphorylation in vitro J. Cell Sci., January 11, 1998; 111(21): 3189 - 3196. [Abstract] [PDF]
|
|
|
|
|
|
X He, M. Jones, M Winey, and S Sazer Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe J. Cell Sci., January 6, 1998; 111(12): 1635 - 1647. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Skoufias, P. R. Andreassen, F. B. Lacroix, L. Wilson, and R. L. Margolis Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints PNAS, April 10, 2001; 98(8): 4492 - 4497. [Abstract] [Full Text] [PDF]
|
|
