Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A foot in the door to genetic information

07.03.2012
In the cell nucleus, DNA wraps around what are called histone proteins, forming regularly spaced spherical bodies called nucleosomes.

Thus, large portions of the genetic material are inaccessible to the gene reading machinery. Scientists at the German Cancer Research Center have now simulated at high time resolution how short DNA segments repeatedly detach spontaneously from the nucleosome. The group has been the first to demonstrate that the spool-shaped histone proteins have an active role in opening access to the genetic information.

Histones are evolutionary highly conserved proteins which are much the same in man, mouse or threadworm. They serve as coils around which the DNA molecule, a thread of several feet, wraps in the cell nucleus. Up until recent years, histones were believed to be little more than DNA packaging material. However, by now it is known that they also determine which genes are read and which are not read; thus, they actively participate in regulating many cell functions.

At DKFZ, Professor Dr. Jörg Langowski is studying the interactions of DNA and its "packaging" at a molecular level. "For DNA to be read it must be at least temporarily accessible. We wanted to find out how and, more importantly, for how long histones and DNA thread disassociate from their tightly wrapped state. This gives us a better understanding of how DNA is read and how this mechanism may possibly be disrupted in cancer cells," says Langowski, outlining the goal of his recently published research.

The packaging of DNA in the cell nucleus is extremely well studied: Each DNA spool consists of two molecules each of four different histone proteins. In each nucleosome, a DNA thread of 146 base pairs wraps around this spherical histone complex exactly 1.75 times. A small stretch of unwrapped DNA of variable length is followed by the next histone spool, forming a structure that looks like beads on a string. Prior studies have suggested that there must be a balance of "wrapped" and unwrapped DNA in the cell nucleus.

Langowski and his coworkers have now been able to resolve these interactions at a highly precise timescale using a novel computer simulation. The researchers observed two different spontaneously occurring open states of which the longer-lived one lasts one hundred thousandth of a second, while the shorter-lived one, during which exactly nine DNA building blocks dissociate from the nucleosome, lasts no more than a few millionths of a second. The group discovered that in both cases the free end of the H3 histone actively moves between protein core and DNA, thus detaching short DNA segments. The investigators assume that once the DNA segments are released from the protein binding, more segments of the DNA thread can be unwrapped more easily.

An interesting observation in this context is that the cell attaches a multitude of chemical, or what is called epigenetic, tags to exactly this free end of the H3 histone. These tags – which are often altered in tumor cells – have an influence on which genes are read and which are not. "Our observations now also confirm at an atomic level that the H3 tail plays a key role in determining when DNA is accessible and genes can be read and when this is not the case. It is what you could call a foot in the door to access the genetic information," said Langowski interpreting his results.

Karine Voltz, Joanna Trylska, Nicolas Calimet, Jeremy C. Smith and Jörg Langowski: Unwrapping of Nucleosomal DNA Ends: A Multiscale Molecular Dynamics Study. Biophysical Journal 2012, DOI:10.1016/j.bpj.2011.11.4028

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful.

Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg where promising approaches from cancer research are translated into the clinic. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. The center is a member of the Helmholtz Association of National Research Centers. Ninety percent of its funding comes from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

Dr. Sibylle Kohlstaedt | EurekAlert!
Further information:
http://www.dkfz.de

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

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 “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>