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?
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!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences