Featured Research

from universities, journals, and other organizations

Study upends model of how dividing cells monitor distribution of chromosomes

Date:
April 21, 2013
Source:
Ludwig Institute for Cancer Research
Summary:
A recent study upends the model for how dividing cells monitor the equal distribution of their chromosomes —- a process that often runs awry in cancer. By targeting Aurora B kinase, their discovery has overturned the prevailing model of advanced cell division.

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 chromatids -- roughly 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.

This work was supported by the Ludwig Institute for Cancer Research, the National Institutes of Health (GM074215) and the Damon Runyon Cancer Research Foundation Fellowship (DRG 2007-09).


Story Source:

The above story is based on materials provided by Ludwig Institute for Cancer Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Christopher S. Campbell and Arshad Desai. Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature, 2013 DOI: 10.1038/nature12057

Cite This Page:

Ludwig Institute for Cancer Research. "Study upends model of how dividing cells monitor distribution of chromosomes." ScienceDaily. ScienceDaily, 21 April 2013. <www.sciencedaily.com/releases/2013/04/130421151620.htm>.
Ludwig Institute for Cancer Research. (2013, April 21). Study upends model of how dividing cells monitor distribution of chromosomes. ScienceDaily. Retrieved July 26, 2014 from www.sciencedaily.com/releases/2013/04/130421151620.htm
Ludwig Institute for Cancer Research. "Study upends model of how dividing cells monitor distribution of chromosomes." ScienceDaily. www.sciencedaily.com/releases/2013/04/130421151620.htm (accessed July 26, 2014).

Share This




More Plants & Animals News

Saturday, July 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How to Make Single Serving Smoothies: Howdini Hacks

How to Make Single Serving Smoothies: Howdini Hacks

Howdini (July 24, 2014) Smoothies are a great way to get in lots of healthy ingredients, plus they taste great! Howdini has a trick for making the perfect single-size smoothie that will save you time on cleanup too! All you need is a blender and a mason jar. Video provided by Howdini
Powered by NewsLook.com
Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Newsy (July 24, 2014) A new study claims a set of prehistoric T-Rex footprints supports the theory that the giant predators hunted in packs instead of alone. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins