Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UVa researchers describe method of protecting chromosomes during cell division

05.03.2004


One hallmark of most cancer cells is that they have the incorrect number of chromosomes, a state called aneuploidy. Now, researchers at the University of Virginia Health System, writing in a recent issue of the journal Current Biology, think they know how cells protect themselves from aneuploidy when they divide in a process known as mitosis. "During mitosis, the cell divides replicated chromosomes to two daughter cells. We are studying a mitotic system that ensures that each cell receives the right number of chromosomes," said article co-author Todd Stukenberg, assistant professor of biochemistry and molecular genetics at U.Va.



To function effectively, a human cell must have one copy of 46 different chromosomes, each containing two exact copies of a long DNA strand packaged into two sister chromatids. When a cell divides, it forms a spindle made up of thin polymers called microtubules extending from opposing sides of the cell.

During division, however, the cell is faced with a monumental sorting problem since all chromosomes look alike. So, nature has devised a solution – microtubules from one side of the cell must bind one chromatid, while microtubules from the other side bind the other. The cell then uses these microtubule connections to pull the two sister chromatids to opposite sides of the cell, and the cell is then cleaved between the two DNA masses. Aneuploidy may occur when this process goes awry and microtubules from opposite sides of the cell bind the same chromatid, which becomes stuck since it is pulled in both directions, Stukenberg said.


According to the study, researchers at the U.Va.’s Department of Biochemisty and Molecular Genetics, working with colleagues in U.Va.’s Department of Chemistry, have uncovered a mechanism that could correct these improper attachments – proteins that release improper microtubule attachments. A protein called Aurora B loads a substance called MCAK (mitotic centromere-associated kinesin) onto the chromosome in an inactive state. When a microtubule from the wrong side of the cell binds a chromatid, MCAK is activated and removes the improperly attached microtubule.

"Aurora B is a regulatory protein that has been previously implicated in this process," Stukenberg said. "It is very satisfying to find that a protein which it is regulating has the enzymatic activity required to remove improperly-attached microtubules. Many questions remain, however, and we at U.Va. are focusing on how MCAK is activated by improper attachments."

Aurora B is a kinase that regulates proteins by modifying amino acids. The researchers identified the specific amino acid on MCAK that was modified by Aurora B, and showed that the modification regulates MCAK activity. Cell injection studies showed the sites where this modification happens, which is crucial for the correct attachment of chromatids and microtubules during mitosis. The researchers also stained cells by immunofluorescence with antibodies to MCAK, phosphorylated MCAK and Aurora B, suggesting that Aurora B regulates MCAK to destroy incorrectly attached microtubules.

Early in the 20th century, some scientists proposed that aneuploidy may be one cause of cancer, Stukenberg said, but that theory was largely ignored for many years.

Now, recent research has "reinvigorated the theory," he said. "So it is important to study whether mutations in Aurora, MCAK or the inability to resolve improper microtubule attachments, is involved in tumor genesis. It is already clearly established that the Aurora family of kinases is overexpressed in many cancerous solid tumors."


Contributing to the study were the Department of Pathology at U.Va., and the Departments of Biology, Biochemistry and Molecular Biology, and Anatomy and Cell Biology at Indiana University.

Bob Beard | EurekAlert!
Further information:
http://hsc.virginia.edu/news

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>