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 Molecular evolution: How the building blocks of life may form in space
26.04.2018 | American Institute of Physics

nachricht Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Why we need erasable MRI scans

New technology could allow an MRI contrast agent to 'blink off,' helping doctors diagnose disease

Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

World's smallest optical implantable biodevice

26.04.2018 | Power and Electrical Engineering

Molecular evolution: How the building blocks of life may form in space

26.04.2018 | Life Sciences

First Li-Fi-product with technology from Fraunhofer HHI launched in Japan

26.04.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>