spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

doi: 10.1242/10.1242/jcs.00029

This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JCS
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhou, J.
Right arrow Articles by Joshi, H. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, J.
Right arrow Articles by Joshi, H. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Attachment and tension in the spindle assembly checkpoint

Jun Zhou, Joyce Yao and Harish C. Joshi*

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA



View larger version (22K):

[in a new window]
  		Fig. 1. The spindle assembly checkpoint acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis. During prophase, the duplicated interphase chromatin condenses into chromosomes (blue) within the nucleus. Simultaneously, the radial array of microtubules (black lines) disappears, and a bipolar array (the mitotic spindle) forms by microtubules emanating from two opposite poles (green) defined by the previously duplicated and now separated pair of centrosomes. Subsequently, the nuclear envelope breaks downs marking the initiation of prometaphase. During this stage, the kinetochores (red) on chromosomes encounter and capture spindle microtubules. When a chromosome becomes attached by microtubules from two opposite spindle poles, it congresses to the equatorial plane (the metaphase plate). In the presence of an intact spindle assembly checkpoint, anaphase onset is triggered when and only when all the chromosomes are attached via kinetochores by microtubules from two spindle poles and correctly aligned at the equatorial plane, a stage referred to as metaphase. However, in cells that have defective spindle assembly checkpoint, anaphase onset is triggered prematurely despite the presence of unattached or improperly attached chromosomes, resulting in missing or extra chromosomes (aneuploidy) in the daughter cells.

 


View larger version (68K):

[in a new window]
  		Fig. 2. Spindle assembly checkpoint signaling. In the presence of unattached or improperly attached kinetochores, the spindle assembly checkpoint is switched on (upper panel). Unattached kinenetochores act as catalytic sites for the activation of Mad2. Activated Mad2 (Mad2*) then diffuses and prevents anaphase onset by inhibiting the activity of Cdc20-APC. In addition, BubR1 functions synergistically with Mad2 in inhibiting Cdc20-APC activity. After all the chromosomes are properly attached by kinetochore microtubules and aligned at the metaphase plate, the spindle assembly checkpoint is turned off (bottom panel). Mad2* is no longer generated, and BubR1 does not interact with Cdc20-APC, resulting in the activation of Cdc20-APC. Activated Cdc20-APC catalyzes the ubiquitination of securin, leading to its degradation through proteosome-mediated proteolysis. Degradation of securin in turn causes the release of separin. The free separin is then able to cleave the SCC1 subunit of the sister-chromatid cohesion complex, triggering the separation of sister chromatids and the onset of anaphase.

 


View larger version (11K):

[in a new window]
  		Fig. 3. Tension develops across sister kinetochores (red) upon their bipolar attachment by spindle microtubules (black line). The paired sister kinetochores are not under tension when they are not attached by spindle microtubules (A) and are under little or no tension when one or both of them are attached by microtubules from one spindle pole (green) (B). However, when microtubules from two opposite spindle poles attach to the sister kinetochores, tension develops across the paired kinetochores owing to the mitotic force that tends to pull the sister chromatids toward two opposite poles against the cohesive force that holds sister chromatids together (C). The level of tension is reflected by an increase in the distance between the paired sister kinetochores.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2002