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 When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>