On rare occasions, its building blocks "rock and roll," deforming the familiar double helix into a different shape.
"We show that the simple DNA double helix exists in an alternative form---for one percent of the time---and that this alternative form is functional," said Hashim M. Al-Hashimi, who is the Robert L. Kuczkowski Professor of Chemistry and Professor of Biophysics at U-M. "Together, these data suggest that there are multiple layers of information stored in the genetic code." The findings were published online Jan. 26 in the journal Nature.
It's been known for some time that the DNA molecule can bend and flex, something like a rope ladder, but throughout these gyrations its building blocks---called bases---remain paired up just the way they were originally described by James Watson and Francis Crick, who proposed the spiral-staircase structure in 1953. By adapting nuclear magnetic resonance (NMR) technology, Al-Hashimi's group was able to observe transient, alternative forms in which some steps on the stairway come apart and reassemble into stable structures other than the typical Watson-Crick base pairs.
The question was, what were these alternative stable structures?
"Using NMR, we were able to access the chemical shifts of this alternative form," said graduate student Evgenia Nikolova. "These chemical shifts are like fingerprints that tell us something about the structure." Through careful analysis, Nikolova realized the "fingerprints" were typical of an orientation in which certain bases are flipped 180 degrees.
"It's like taking half of the stairway step and flipping it upside down so that the other face now points up," said Al-Hashimi. "If you do this, you can still put the two halves of the step back together, but now what you have is no longer a Watson-Crick base pair; it's something called a Hoogsteen base pair."
"Using computational modeling, we further validated that individual bases can roll over inside the double helix to achieve these Hoogsteen base pairs," said Ioan Andricioaei, an associate professor of chemistry at the University of California, Irvine.
Hoogsteen base pairs have previously been observed in double-stranded DNA, but only when the molecule is bound to proteins or drugs or when the DNA is damaged. The new study shows that even under normal circumstances, with no outside influence, certain sections of DNA tend to briefly morph into the alternative structure, called an "excited state."
Previous studies of DNA structure have relied mainly on techniques such as X-ray and conventional NMR, which can't detect such fleeting or rare structural changes.
"These methods do not capture alternative DNA structural forms that may exist for only a millisecond or in very little abundance, such as one percent of the time," said Al-Hashimi. "We took new solution NMR methods that previously have been used to study rare deformations in proteins and adapted them so that they could be used to study rare states in nucleic acids. Now that we have the right tools to look at these so-called excited states, we may find other short-lived states in DNA and RNA."
Because critical interactions between DNA and proteins are thought to be directed by both the sequence of bases and the flexing of the molecule, these excited states represent a whole new level of information contained in the genetic code, Al-Hashimi said.
In addition to Al-Hashimi, Nikolova and Andricioaei, the paper's authors are undergraduate student Abigail Wise and assistant professor of biological chemistry Patrick O'Brien of U-M and postdoctoral researcher Eunae Kim of the University of California, Irvine.
The researchers received funding from the National Science Foundation, the National Institutes of Health and the University of Michigan.
Hashim Al-Hashimi: https://www.chem.lsa.umich.edu/chem/faculty/facultyDetail.php?Uniqname=hashimi
Nancy Ross-Flanigan | Newswise Science News
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
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...
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...
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....
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,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses