Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key Mechanism in Genetic Inheritance During Cell

02.02.2005


A key mechanism in the passing of genetic material from a parent cell to daughter cells appears to have been identified by a team of Berkeley researchers. Their study may explain how a complex of proteins, called kinetochores, can recognize and stay attached to microtubules, hollow fibers in the walls of biological cells that are responsible for the faithful segregation of chromosomes during cell division.


Kinetochore proteins bind to a microtubule spindle to keep chromosomes segregated during cell division. This segregation is critical for preventing mistakes that can lead to cancer and birth defects.



“In test tube experiments, we’ve found that the kinetochore proteins form rings around the microtubules and this ring formation promotes microtubule assembly, stabilizes against disassembly, and promotes bundling,” says Eva Nogales, a biophysicist who holds joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab), the University of California at Berkeley, and the Howard Hughes Medical Institute (HHMI). “If ring formation takes place in vivo, it could be the mechanism by which chromosomes are kept segregated during mitosis.”

Nogales is one of the co-authors of a paper reporting the results of this research which appears in the January 21, 2005 issue of the journal Molecular Cell. Other authors of the Molecular Cell paper were Georjana Barnes, David Drubin and Stefan Westermann, with UC Berkeley’s Department of Molecular and Cell Biology, who were the lead investigators on this work, plus Agustin Avila-Sakar and Hong-Wei Wang, with Berkeley Lab, and Hanspeter Niederstrasser and Jonathan Wong with UC Berkeley.


Says Barnes, “Mistakes in chromosome segregation during mitosis contribute to cancer and birth defects. From various genetic experiments we know that the activity of a 10-protein complex of kinetochores, called Dam1, is responsible for the faithful segregation of chromosomes during mitosis. While we don’t know at this time that ring formation occurs in vivo, we do see in our in vitro tests that Dam1 ring formation strengthens the microtubules.”

Thousands of microtubule fibers are woven together to form a highly flexible cytoskeleton in biological cells that gives shape to cell walls and other structures, and controls the transportation of substances in and out of a cell. During cell division (mitosis), the microtubule fibers disassemble and reform into spindles across which duplicate sets of chromosomes line up. During this phase, it is critical that the spindles maintain their structural integrity so that they can segregate a single copy of each chromosome to each daughter cell. After which, the microtubules again disassemble and reform back into skeletal systems for the two new daughter cells. It has been determined, through the genetic research of Barnes and Drubin, among others, that kinetochores must bind to a microtubule spindle to avoid the gain or loss of chromosomes by each of the daughter cells. How this works, however, was unknown.

To find answers, the Berkeley researchers used a purified, reconstituted Dam1 complex, obtained from genetically engineered E. coli bacteria, and compared its effects on microtubules in vitro to the effects caused by certain Dam1 mutants. Their analysis shed new light on the structural nature of the kinetochore-microtubule interface, and may provide a biochemical explanation for the role of kinetochores in maintaining chromosome segregation during mitosis.

“Our studies indicate that the Dam1 rings are formed by longitudinal self-assembly of multiple copies of the Dam1 complex upon the microtubule surface,” the authors state in their Molecular Cell paper. “Although the presence of microtubules strongly facilitates the oligomerization process, ring assembly seems to be an intrinsic property of the Dam1 complex, as we have been able to induce self-assembly into rings in the absence of microtubules.”

The formation of rings around the microtubules by the purified Dam1 complex that the Berkeley collaborators observed has not been reported for any other microtubule binding protein complex. While the authors say that ring formation is a complicated way to construct a microtubule binding structure, a microtubule binding ring might be uniquely suited to fulfill the functions of the Dam1 complex. In comparison with the purified Dam1, the Dam1 mutants produced partially formed rings that reduced microtubule binding.

“Because the stability of a microtubule is thought to be largely governed by the lateral interactions between adjacent protofilaments,” the authors note, “rings that bind orthogonally to the microtubule axis are not only expected to strengthen interprotofilament interactions, but to also prevent protofilament peeling, which in turn would encourage further growth.

Furthermore, the Berkeley researchers showed that binding between the ring and the microtubule is mediated by flexible domains, and is largely electrostatic in nature. This could allow for lateral sliding or diffusion of Dam1 rings along microtubules. Analysis of the Dam1 rings after disassembly of microtubules, revealed an accumulation of rings at the ends of the microtubule, suggesting that the rings do not disassemble but slide back as the microtubule protofilaments peel away from the ends.

Says Nogales, “That the rings remain attached to the microtubule end as it depolymerizes, is a most ingenious mechanism to move chromosome to the two daughter cells during anaphase, without even requiring energy. This is great finding!”

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

Lynn Yarris | EurekAlert!
Further information:
http://www.lbl.gov

More articles from Life Sciences:

nachricht Good preparation is half the digestion
15.11.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht How the gut ‘talks’ to brown fat
16.11.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Massive impact crater from a kilometer-wide iron meteorite discovered in Greenland

15.11.2018 | Earth Sciences

When electric fields make spins swirl

15.11.2018 | Physics and Astronomy

Discovery of a cool super-Earth

15.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>