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:11/19/2016)... , Nov. 18, 2016 Securus Technologies, ... solutions for public safety, investigation, corrections and monitoring, announced ... smaller competitor, ICSolutions, to have an independent technology judge ... the most modern high tech/sophisticated telephone calling platform, and ... customers that they do most of what we do ...
(Date:11/15/2016)...  Synthetic Biologics, Inc. (NYSE MKT: SYN), a ... gut microbiome, today announced the pricing of an ... common stock and warrants to purchase 50,000,000 shares ... the public of $1.00 per share and accompanying ... offering, excluding the proceeds, if any from the ...
(Date:6/27/2016)... Research and Markets has announced the addition of the ... The report forecasts the biometrics ... a CAGR of 12.28% during the period 2016-2020. ... with inputs from industry experts. The report covers the market landscape ... includes a discussion of the key vendors operating in this market. ...
Breaking Biology News(10 mins):
(Date:12/2/2016)... MA (PRWEB) , ... December 02, 2016 , ... Robots ... Light Event on December 3rd, 2016. The event, which is held on the ... work with helping Americans with Disabilities back into the workplace. Suitable Technologies is partnering ...
(Date:12/2/2016)... December 2, 2016 The immunohistochemistry (IHC) ... at a CAGR of 7.3% during the forecast period of 2016 ... diagnostic laboratories segment accounted for the largest share of immunohistochemistry (IHC) ... , ... global immunohistochemistry (IHC) market spread across 225 pages, profiling 10 companies ...
(Date:11/30/2016)... ... November 30, 2016 , ... BEI Kimco, a brand ... a flexure design that ensures high alignment accuracy by preventing unwanted shaft rotation. ... suited where extreme precision is required, such as in medical equipment, laboratory instrumentation, ...
(Date:11/30/2016)... , November 30, 2016 ... a few players hold a dominant share in the ... River Laboratories International, Inc., and Merck KGaA, held a ... 2015. Transparency Market Research observes that these companies are ... on development products that are do not require rabbit ...
Breaking Biology Technology: