Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure determined for key molecular complex involved in long-term gene storage

19.09.2006
Genome-management system seen as a natural protection against cancer

Around the home, regularly used tools are generally kept close at hand: a can opener in a kitchen drawer, a broom in the hall closet. Less frequently used tools are more likely to be stored in less accessible locations, out of immediate reach, perhaps in the basement or garage. And hazardous tools might even be kept under lock and key.

Similarly, the human genome has developed a set of sophisticated mechanisms for keeping selected genes readily available for use while other genes are kept securely stored away for long periods of time, sometimes forever. Candidate genes for such long-term storage include those required only for early development and proliferation, potentially dangerous genes that could well trigger cancers and other disorders should they be reactivated later in life. Cancer researchers and others have been eager to learn more about the molecules that direct this all-important system for managing the genome.

Now, researchers at The Wistar Institute and Fox Chase Cancer Center have successfully determined the three-dimensional structure of a key two-molecule complex involved in long-term gene storage, primarily in cells that have ceased proliferating, or growing. The study also sheds light on a related two-molecule complex that incorporates one member of the molecular pair, but with a different partner. This second complex is involved in storing genes in a more accessible way in cells that continue to grow. A report on the team's findings, published online on September 17, will appear in the October issue of Nature Structural and Molecular Biology.

... more about:
»Asf1 »Chromatin »Key »Molecular »Molecules

"The two-molecule complex we studied is pivotal for protecting certain genes from expression, genes that could cause problems if they were activated," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and one of the two senior authors on the study. "This is the first time we've been able to see the structure of these molecules communicating and interacting with each other, and it provides important insights into their function."

"By defining some of the rules that dictate how these complexes are formed and operate, we have revealed a part of the difference between growing and non-growing cells," says Peter D. Adams, Ph.D., an associate member in the Basic Science Division at Fox Chase and the other senior author on the study. "This difference is crucial to the distinction between normal and cancerous cells and may inform our ability to treat this disease."

The molecular complex studied by the scientists governs the assembly of an especially condensed form of chromatin, the substructure of chromosomes. The complex is called a histone chaperone complex, responsible for inserting the appropriate histones into the correct locations within the chromatin. Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin.

"There are more and less condensed forms of chromatin," explains Marmorstein. "The less condensed forms correlate with more gene expression, and the more condensed forms involve DNA that's buried away and is not transcribed."

"Appropriate packaging of the DNA in the cell nucleus is crucial for proper functioning of the cell and suppression of disease states, such as cancer," says Adams.

An unanticipated observation from the study centers on the region of association between the two molecules in the complex. The researchers knew that one of the two molecules in the complex, called ASF1, associated with a particular molecular partner, HIRA, when directing assembly of the more condensed form of chromatin. But it could also associate with a different partner, called CAF1, to shepherd assembly of the less condensed form of chromatin.

On closer study, the scientists discovered that HIRA and CAF1 have nearly identical structural motifs in the regions of interaction with ASF1. This means that ASF1 can bind to one or the other molecular partner, but not to both. In other words, the interaction is mutually exclusive: A kind of decision is made by ASF1 as to whether to guide the assembly process towards the more or less condensed forms of chromatin. What determines the choice? The relevant factors are unknown for now.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.org

Further reports about: Asf1 Chromatin Key Molecular Molecules

More articles from Life Sciences:

nachricht Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>