Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How a molecular Superman protects the genome from damage

17.10.2014

Scientists find a new role for RNAi protein Dicer in preventing collisions during DNA replication

How many times have we seen Superman swoop down from the heavens and rescue a would-be victim from a rapidly oncoming train?

How Dicer Protects the Yeast Genome from Damage

CSHL scientists have found a new role for the RNAi protein Dicer in preserving genomic stability in yeast. Dicer helps prevent collisions between transcription and replication machinery as the genetic material is copied. In cells that lack Dicer, DNA damage accumulates strikingly (yellow spots in the cells above), leading to DNA rearrangements that are associated with aging and disease.

Credit: Cold Spring Harbor Laboratory/ Jie Ren and Stephen Hearn

It's a familiar scenario, played out hundreds of times in the movies. But the dramatic scene is reenacted in real life every time a cell divides. In order for division to occur, our genetic material must be faithfully replicated by a highly complicated machine, whose parts are tiny enough to navigate among the strands of the double helix.

The problem is that our DNA is constantly in use, with other molecular machines continually plucking at its strands to gain access to critical genes. In this other process, known as transcription, the letters of our DNA are being copied to form a template that will guide the formation of proteins. But these two copying machines can't occupy the same bit of genetic track at once. Inevitably they will collide – unless a molecular Superman can remove the transcription machinery and save the day.

Cold Spring Harbor Laboratory (CSHL) scientists have found that this molecular Superman exists in the form of a protein known as Dicer. Better known for its role in selectively silencing genes via a process called RNA interference (RNAi), Dicer is now understood to help free transcription machinery from DNA so that replication can occur.

The team, led by Robert Martienssen, a CSHL Professor and Howard Hughes Medical Institute Investigator, concludes that this previously unknown function of Dicer is critical to preserve the integrity of the genome in yeast. They point out that collisions between the replication and transcription machinery lead to massive changes across the genome – changes that are associated with aging and diseases like cancer.

Martienssen and his colleagues previously found that RNAi resolves the conflict between transcription and DNA replication in isolated areas of the genome where genes are being silenced. "When Dicer is mutated, replication stalls and DNA in the region becomes damaged," explains Martienssen. "This was a new role for a protein that we thought functioned solely in RNAi."

In work published today in Cell, Martienssen and his team explored if and how Dicer might function more broadly, across the entire genome. The team, including lead authors Stephane Castel, Ph.D., a graduate of the CSHL Watson School of Biological Sciences, and Jie Ren, Ph.D., a postdoctoral researcher, found that Dicer participates in the release of transcription machinery throughout the genome. "Dicer's function isn't restricted to silenced genes," explains Ren. In fact, it controls the release at hundreds of extremely active genes.

"These are genes that are in constant use by the cell – we call many of them 'housekeeping' genes because they are required for basic survival," says Castel. At any given time, transcription machinery can be found near these genes. Without the help of Dicer, this machinery is headed for an almost certain collision when replication occurs.

Are these collisions really so catastrophic for the cell? The team found that the accidents cause massive segments of DNA to be lost with each cell division. "These chromosome rearrangements, known as genomic instability, are involved in aging and cancer," says Ren. Other groups have shown that mutations in Dicer are similarly associated with an increased risk of tumor formation. The team's discovery may help to explain these observations, according to Martienssen. "It may be that Dicer's role in cancer is to protect the genome by preventing collisions between transcription and replication."

This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Spanish Ministerio de Economía y Competitividad, the National Institutes of Health, the Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, as well as a Cashin Scholarship from the Watson School of Biological Sciences and assistance from the Cold Spring Harbor Laboratory Shared Resources, which are funded in part by the Cancer Center Support Grant.

"Dicer Promotes Transcription Termination at Sites of Replication Stress to Maintain Genome Stability" appears online in Cell on October 16, 2014. The authors are: Stephane Castel, Jie Ren, Sonali Bhattacharjee, An-Yun Chang, Mar Sánchez, Alberto Valbuena, Francisco Antequera, and Robert Martienssen. The paper can be obtained online at: http://www.cell.com

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu

Jaclyn Jansen | Eurek Alert!

Further reports about: DNA Laboratory RNAi collisions damage function genes replication transcription

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>