Navigation Links
A check on tension
Date:4/21/2013

April 21, 2013, New York, NY and San Diego Calif. Ludwig researchers Arshad Desai and Christopher Campbell, a post-doctoral fellow in his laboratory, were conducting an experiment to parse the molecular details of cell division about three years ago, when they engineered a mutant yeast cell as a control that, in theory, had no chance of surviving. Apparently unaware of this, the mutant thrived.

Intrigued, Campbell and Desai began exploring how it had defied its predicted fate. As detailed in the current issue of Nature, what they discovered has overturned the prevailing model of how dividing cells ensure that each of their daughter cells emerge with equal numbers of chromosomes, which together package the genome. "Getting the right number of chromosomes into each cell is absolutely essential to sustaining life," explains Desai, PhD, a Ludwig member at the University of California, San Diego, "but it is also something that goes terribly wrong in cancer. The kinds of mistakes that occur when this process isn't functioning properly are seen in about 90% of cancers, and very frequently in advanced and drug-resistant tumors."

Campbell and Desai's study focused in particular on four interacting proteins known as the chromosomal passenger complex (CPC) that monitor the appropriate parceling out of chromosomes. When cells initiate division, each chromosome is made of two connected, identical sister chromatidsroughly resembling a pair of baguettes joined in the middle. As the process of cell division advances, long protein ropes known as microtubules that extend from opposite ends of the cell hook up to the chromosomes to yank each of the sister chromatids in opposite directions. The microtubules attach to the chromatids via an intricate disc-like structure called the kinetochore. When the protein ropes attach correctly to the sister chromatids, pulling at each from opposing sides, they generate tension on the chromosome. One of the four proteins of the CPC, Aurora B kinase, is an enzyme that monitors that tension. Aurora B is expressed at high levels in many cancers and has long been a target for the development of cancer therapies.

Aurora B is essentially a molecular detector. "If the chromosomes are not under tension," says Desai, "Aurora B forces the rope to release the kinetochore and try attaching over and over again, until they achieve that correct, tense attachment."

The question is how? Aurora B is ordinarily found between the two kinetochores in a region of the chromosome that links the sister chromatids, known as the centromere. The prevailing model held that the microtubule ropes would pull themselves, and the kinetochores, away from Aurora B's reach, so that it cannot force the microtubule ropes to detach from their captive chromosomes. In other words, the location of Aurora B between the two kinetochore discs was thought to be central to its role as a monitor of the requisite tension. "This matter was thought settled," says Desai.

Yet, as Campbell and Desai show through their experiments, yeast cells engineered to carry a mutant CPC that can't be targeted to the centromere survive quite vigorously. They demonstrate that in such cells Aurora B instead congregates on the microtubule ropes. There, it somehow still ensures that the required tension is achieved on chromosomes before they are parceled out to daughter cells.

How precisely it does this remains unclear. Campbell and Desai provide evidence that the clustering of Aurora B on microtubules might be sufficient to activate its function. At the same time, they hypothesize, appropriate tension on the chromosome may induce structural changes in Aurora B's targets that make them resistant to its enzymatic activity. Campbell and Desai are now conducting experiments to test these ideas.


'/>"/>

Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

Related biology news :

1. New checklist brings information about Cucurbitaceae up to date
2. A new checklist confirms Indian origins of pumpkins and cucumbers
3. As Amazon urbanizes, rural fires burn unchecked
4. UCLA Receives $46 Thousand Check for Groundbreaking Research on Debilitating Pregnancy Disease
5. Discovered a new checkpoint of cell cycle control through joint action of 2 proteins
6. New approach to spell checking gene sequences
7. Americas clean energy policies need a reality check, say Stanford researchers
8. Culprit behind unchecked angiogenesis identified
9. Sodium transporter appears likely target for treating salt-sensitive hypertension
10. OHSU study shows that a molecule critical to nerve cells increases drammatically during hypertension
11. Second-generation drug used for hypertension aids heart function independent of blood pressure
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/11/2016)... CHICAGO , Jan. 11, 2016  higi, ... via nearly 10,000 retail locations, web and mobile, ... than $40 million from existing investors. ... will be devoted to further innovate higi,s health ... app and web portal – including expanding services ...
(Date:1/7/2016)... , Jan. 7, 2016 This BCC Research ... for biometric technologies and devices, identifying newer markets and ... various types of biometric devices. Includes forecast from 2015 ... Identify newer markets and explore the expansion of the ... Examine each type of biometric technology, determine its current ...
(Date:1/6/2016)... 2016  Varam Capital, a provider of micro-finance inclusion ... deliver advanced authentication solutions to their clients. Varam supplies ... A loan of a few thousand rupees may make ... ability to purchase livestock or equipment for a small ... for a local store. ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... N.J. , Feb. 3, 2016 ... totaling more than $1 million for researchers in ... working on health-related research that demonstrates exciting potential. ... round of funding for the New Jersey Health Foundation ... faculty members at these educational institutions— Princeton University, ...
(Date:2/3/2016)... ... 2016 , ... ProMIS Neurosciences is currently in the process ... propagating strains of Amyloid beta involved in Alzheimer’s disease. The Company plans to ... on from the first misfolded Amyloid beta target announced on Nov. 12, 2015, ...
(Date:2/3/2016)... ... February 03, 2016 , ... ... annual report which summarizes and analyzes nearly 750 unique supply chain notifications ... and analysis service. , Supply chain risk management practitioners subscribe to the ...
(Date:2/3/2016)... Feb. 3, 2016  Today, Symphony Technology Group (STG) ... , a leading provider of primary research and analytics-based ... IMS Health , a global information and technology services ... and technologies will be integrated into IMS Health to ... market research capabilities. ...
Breaking Biology Technology: