Essential cell division zipper anchors to so-called junk DNA
Mechanism may provide insights into development and cancer
When cells divide in two, they must carefully manage the process by which their DNA is replicated and then apportioned to the daughter cells. In one critical step along the way, the replicated DNA strands - or sisters - are held together for a period by a temporary scaffold of bridging proteins. When the timing is right, the proteins unzip, allowing the DNA sisters to separate. Errors in this or other steps in cell division can lead to cell death, faulty development, or cancer, which is largely defined as misregulated cell division.
Scientists have had a number of questions about these important bridging proteins, called cohesins. For example, how and where do the proteins attach themselves to the DNA? To protect genes from inappropriate activation, DNA is tightly wrapped around small proteins called histones and then further coiled into a higher structure called chromatin that serves as an effective accessibility barrier to the genes.
In a new study in the August 29 issue of Nature, researchers at The Wistar Institute identify a cohesin-containing protein complex that reshapes chromatin to allow cohesins to bind to DNA. In doing so, they also identified the locations on the human genome where the cohesins bind. Somewhat to their surprise, the binding sites were found to be a repetitive DNA sequence found throughout the human genome for which no previous role had ever been identified. These bits of DNA, known as Alu sequences, are liberally represented along those vast stretches of the human genome not known to directly control genetic activity, sometimes referred to as junk DNA.
"One thing that interested us is that there are 500 thousand to 1 million Alu repeats across the human genome," says Ramin Shiekhattar, Ph.D., an associate professor at The Wistar Institute and senior author on the Nature study. "These sequences are very common. And this makes sense if one of their roles is to bind to the bridging proteins, the cohesins, to keep the replicated DNA sisters together until it is time for them to separate. Multiple bridging sites throughout the DNA would be needed for this system to work. They couldnt be unique sequences."
In their investigations, Shiekhattar and his coworkers noticed that many, but not all the Alu sequences bound cohesin, and they wondered what rules might govern the process. Additional experiments revealed that if the histone proteins were methylated and acetylated - that is, if a methyl and acetyl molecule were bound to them - then the chromatin structure relaxed to allow access to the DNA. But if the Alu sequence on the DNA was itself methylated, then the cohesin could not bind to the DNA at that site.
Why these modifications might take place at some Alu sites and not others was not clear. But, taken together, the research teams observations are supportive of the existence of what some scientists have termed a "histone code." This recently proposed theory suggests that a system of complex, interdependent modifications to histones is responsible for regulating access to DNA and genes.
"The idea that a kind of code of modifications to the molecular packaging of DNA may govern gene activity is an intriguing one," Shiekhattar says. "If we were to better understand this code, it might provide us with important insights into diseases tied to problems in gene control, including developmental disorders and cancer. These are some of the questions were looking into now, using this study as a starting point."
Franklin Hoke | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
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...