A mother's touch may protect against drug cravings later

An attentive, nurturing mother may be able to help her children better resist the temptations of drug use later in life, according to a study in rats conducted by Duke University and the University of Adelaide in Australia.

A rat mother's attention in early childhood actually changes the immune response in the brains of her pups by permanently altering genetic activity, according to Staci Bilbo, an assistant professor of psychology and neuroscience at Duke, who led the research. High-touch mothering increased the brain's production of an immune system molecule called Interleukin-10, leaving these rats better able to resist the temptation of a dose of morphine much later in life.

This is the first study to show how morphine causes a molecular response in the glial cells of the brain's reward centers, which had only recently been identified as part of drug addiction's circuitry. "We set out to find out what that response looks like," Bilbo said.

To program some of the rat pups to produce more IL-10, the researchers used an established technique called the "handling paradigm," in which very young rat pups are removed from their mother's cage for 15 minutes and then returned. "As soon as they're returned, she checks them out vigorously," grooming the pups and cleaning them, Bilbo said. For a control group, another set of pups were never removed. Some of them had more attentive mothers than others, just by natural variation.

The animals then were put through a test called the "place preference chamber," a two-roomed cage in which they would be given a dose of morphine if they entered one side, or a dose of saline on the other. Over the next four weeks, the rats were returned to the two-sided chamber three times a week for five minutes, but were never given another dose of morphine. Initially, they all showed a preference for the morphine side, but over time, the handled rats showed little preference, which indicated their craving had been "extinguished," Bilbo said.

About 8 weeks after their first exposure to morphine, the animals were each given a very small dose of morphine to prime craving and then returned to the 2-sided chamber. The non-handled control rats preferred spending time in the morphine chamber; the handled rats still showed no clear preference.

Morphine activates the glial cells of the brain to produce inflammatory molecules which signal a reward center of the brain called the nucleus accumbens. But IL-10 works against that inflammation and reward. The more IL-10 the brain produces, the less likely morphine would cause an increase in craving or relapse weeks after the initial experience with the drug.

The brains of the rat pups who experienced high-touch mothering were found to have more active genes for producing IL-10 in the microglial cells of the brain, which apparently "completely knocked out this drug-seeking behavior," Bilbo said. They were producing about four times as much IL-10 as the control animals. "The nurturing moms can profoundly change outcomes," Bilbo said.

This is a change not of the genes themselves, but of the way they are controlled by something called methylation, which can keep a gene's activity suppressed. High-touch mothering removed methylation on the IL-10 gene, making these rats produce more of the anti-inflammatory molecule.

To further prove that IL-10 levels were key to the craving, the researchers used a drug called ibudilast to artificially increase IL-10 production in a group of control rats. These rats experience craving extinction much the same as the high-touch rats.

It's important to note that the genetic modification created by the mothering didn't change the initial rewarding effect of the morphine, it altered the craving for that reward much later, Bilbo said.

Bilbo said her team next wants to look at the long-term effects of maternal stress on the brain's immune response. They'll be working with the Children's Environmental Health Initiative at Duke, which examines real-world environmental health effects in Durham, NC in collaboration with the US Environmental Protection Agency.

More information: "Early-Life Experience Decreases Drug-Induced Reinstatement of Morphine CPP in Adulthood via Microglial-Specific Epigenetic Programming of Anti-Inflammatory IL-10 Expression," Jaclyn M. Schwarz, Mark R. Hutchinson and Staci D. Bilbo. The Journal of Neuroscience, Dec. 6, 2011. DOI -10.1523/JNEUROSCI.3297-11.2011

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"A mother's touch may protect against drug cravings later." December 6th, 2011. http://medicalxpress.com/news/2011-12-mother-drug-cravings.html

 

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Psychology researcher finds that power does go to our heads

Power -- defined as the ability to influence others -- makes people think differently. For North Americans, a feeling of power leads to thinking in a focused and analytical way, which may be beneficial when pursuing personal goals.

"What's most interesting about this study is the idea that thinking is flexible, not rigid or innately pre-programmed. We are able to attune our style of thinking to the needs of the situation," explains Li-Jun Ji, the study's co-author and a social psychologist who studies the relationships between culture and thinking. "However, the specific ways we might attune our thinking seems to depend on our cultural background."

For most people, being in a position of power or influence means that you want to influence others and achieve your own goals. In North America, these goals tend to be self-defined and independent from the wider social context. As a result, thinking -- focusing on one's own goal and how to achieve it without being distracted by the surrounding context -- can be advantageous.

Dr. Ji also found that North American individuals with high socioeconomic status (SES) displayed more analytical thinking than low SES individuals. She believes that this may be because higher SES increases people's feelings of agency, a precursor to power.

In order to induce feelings of power, the researchers asked study participants to recollect occasions in their lives when they had influenced others. The kind of memories the participants recalled included making a shy roommate more outgoing, influencing people to buy products as part of a fundraiser, and leading a struggling soccer team to victory.

The participants were then asked to complete a number of different tasks designed to assess whether they were thinking more analytically or more holistically. Analytical thinking is characterized by processing a focal object and its features independently from its surrounding context (for example, using adjectives to describe a ball as 'red' or 'round'). Holistic thinking involves a focus on contextual information and the relationships between objects (for example, using verbs like 'kick' or 'play' to highlight the connection between the ball and its environment).

More information: This research was published in the Personality and Social Psychology Bulletin.

Provided by Queen's University

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Being told painting is fake changes brain's response to art

A self portrait by Rembrandt (1630)

(Medical Xpress) -- Being told that a work of art is authentic or fake alters the brain’s response to the visual content of artwork, Oxford University academics have found.

Fourteen participants were placed in a brain scanner and shown images of works by ‘Rembrandt’ – some were genuine, others were convincing imitations painted by different artists. Neither the participants nor their brain signals could distinguish between genuine and fake paintings. However, advice about whether or not an artwork is authentic alters the brain’s response; this advice is equally effective, regardless of whether the artwork is genuine or not.

The study, published in Frontiers in Human Neuroscience, was carried out by Professor Andrew Parker and Mengfei Huang of the Department of Physiology, Anatomy and Genetics, in collaboration with Dr Holly Bridge at the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) and Professor Martin Kemp of Oxford University’s History Faculty.

Professor Martin Kemp, Emeritus Professor of the History of Art at Oxford University, said: ‘Our findings support what art historians, critics and the general public have long believed – that it is always better to think we are seeing the genuine article. Our study shows that the way we view art is not rational, that even when we cannot distinguish between two works, the knowledge that one was painted by a renowned artist makes us respond to it very differently. The fact that people travel to galleries around the world to see an original painting suggests that this conclusion is reasonable.’

When a participant was told that a work was genuine, it raised activity in the part of the brain that deals with rewarding events, such as tasting pleasant food or winning a gamble. Being told a work is not by the master triggered a complex set of responses in areas of the brain involved in planning new strategies. Participants reported that when viewing a supposed fake, they tried to work out why the experts regarded it not to be genuine.

Andrew Parker, Professor of Physiology at Oxford University and the study’s senior author, said: 'Our findings support the idea that when we make aesthetic judgements, we are subject to a variety of influences. Not all of these are immediately articulated. Indeed, some may be inaccessible to direct introspection but their presence might be revealed by brain imaging. It suggests that different regions of the brain interact together when a complex judgment is formed, rather than there being a single area of the brain that deals with aesthetic judgements.’

Participants were shown a variety of portraits, some genuinely painted by Rembrandt and others not. This was chosen as a good test case, because recent scholarship has determined that many fakes and copies of his works exist. There was no evidence that the brain signals of the participants could reliably pick apart the true Rembrandts from the copies or fakes, so this research will not help to resolve the arguments that sometimes rage among connoisseurs and experts.

FMRIB is a multi-disciplinary neuroimaging research facility, which focuses on the use of Magnetic Resonance Imaging (MRI) for neuroscience research. Functional magnetic resonance imaging (FMRI) measures brain activity by detecting the changes in blood oxygenation and flow that occur in response to neural activity – when a brain area is more active it consumes more oxygen and to meet this increased demand blood flow increases to the active area. FMRI can be used to produce activation maps showing which parts of the brain are involved in a particular mental process.

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Changes in the path of brain development make human brains unique

How the human brain and human cognitive abilities evolved in less than six million years has long puzzled scientists. A new study conducted by scientists in China and Germany, and published December 6 in the online, open-access journal PLoS Biology, now provides a possible explanation by showing that activity levels of genes in the human brain during development changed substantially compared to chimpanzees and macaques. What's more, these changes might be caused by a handful of key regulatory molecules called microRNAs.

The authors studied gene activity in human, chimpanzee and macaque brains across their lifetimes. Starting from newborns, they investigated two brain regions; the cerebellum, which is responsible for motor activity, and the prefrontal cortex, which has roles in more complex behavior such as social interactions or abstract thinking. They first studied the simple gene activity differences between species that are seen at all ages. Although many genes show such simple differences, there was no disparity in numbers of these differences between the human and the chimpanzee evolutionary lineages. Moreover, most of these differences were observed in both of the brain regions studied, and the genes involved are not thought to be specifically involved in brain function. In the opinion of Mehmet Somel, the lead author of the study, these differences represent evolutionary "white noise" and have little importance for human brain evolution.

The authors then looked for changes in gene activity during development, comparing the activity of genes in newborns and adults. In general, brain developmental patterns tend to be quite similar in humans, other primate species, and even mice. Nevertheless, the authors found that for hundreds of genes, humans display unique developmental patterns, with profiles that were different in shape and/or timing from those found in chimpanzees and macaques. Such human-specific developmental gene activity patterns were particularly widespread in the prefrontal cortex, where genes showing human-specific changes outnumbered genes showing chimpanzee-specific changes by four-fold. Developmental patterns in the cerebellum, by contrast, were much less human-specific. Furthermore, many genes displaying these human-specific patterns in the prefrontal cortex were known to have specific neural functions, implying roles in human cognitive development.

Looking for possible causes of this widespread developmental remodeling in the human prefrontal cortex, the authors stumbled upon an unexpected signal. Developmental patterns of genes that encode microRNAs (tiny but powerful regulators that target many other genes and processes) showed even greater excess of human-specific changes in the prefrontal cortex than did comparable developmental patterns in ordinary genes. Several of these changes in microRNA activity could be directly linked to human-specific changes in activity of their target genes. Since each microRNA may regulate the activity of hundreds of other genes, this finding provides a possible explanation to how hundreds of genes changed their activity patterns (in a coordinated way) during human brain development.

This result further implies that the evolution of human cognitive abilities might be traced back to a small number of mutations in key developmental regulators. Philipp Khaitovich, the senior author of the study, suggests that "identifying the exact genetic changes that made us think and act like humans might be easier than we previously imagined". This said, it is likely to require much more work with a focus on the dynamics of brain development and wider use of transgenic mice, and even primate models.

Further to this, the authors point out that identification of the key human-specific DNA mutations could help us to determine how close the Neanderthals' cognitive abilities were to ours. "If Neanderthals' brain development was similar to that of chimpanzees and macaques, it would be no wonder that they became extinct when confronted by Modern Humans," says Mehmet Somel.

More information: Somel M, Liu X, Tang L, Yan Z, Hu H, et al. (2011) MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates. PLoS Biol 9(12): e1001214. doi:10.1371/journal.pbio.1001214

 

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Liver and pancreas precursor cells created using new stem cell production method

Technique should help research into pre-clinical and clinical evaluation of cells 

Scientists in Canada have overcome a key research hurdle to developing regenerative treatments for diabetes and liver disease with a technique to produce medically useful amounts of endoderm cells from human pluripotent stem cells. The research, published in Biotechnology and Bioengineering, can be transferred to other areas of stem cell research helping scientists to navigate the route to clinical use known as the ‘valley of death’.

“One million people suffer from type 1 diabetes in the United States, while liver disease accounts for 45,000 deaths a year,” said Dr Mark Ungrin from the University of Toronto. “This makes stem cells, and the potential for regenerative treatments, hugely interesting to scientists. Laboratory techniques can produce thousands, or even millions, of these cells, but generating them in the numbers and quality needed for medicine has long been a challenge.”

The research focused on the process of using pluripotent stem cells (PSC) to generate endoderm cells, one of the three primary germ layers which form internal organs including the lungs, pancreas, and liver. The ability to differentiate, or transform, PSCs into endoderm cells is a vital step to developing regenerative treatments for these organs.

“In order to produce the amount of endoderm cells needed for treatments it is important to understand how cells behave in larger numbers, for example how many are lost during the differentiation process and if all the cells will differentiate into the desired types,” said Ungrin.

The team stained cells with fluorescent dye and as the cells divided, the dye was shared equally between the divided cells. By measuring the fluorescence of cell populations at a later stage the team were able to work out the frequency of cell division, which allowed them to predict how many cells would be present in a population at any given time.

This technique allowed the team to detect cell inefficiencies and develop a new understanding of the underlying cell biology during the differentiation of PSCs. This allowed the team to increase effective cell production 35 fold.

“Our results showed significant increases in the amount of endoderm cells generated,” said Ungrin. “This new concept allows us to scale up the production of useful cells, while ensuring PSC survival and effective differentiation.”

Overcoming this bottleneck in research will also help future stem cell researchers navigate the often long and challenging route from laboratory testing to clinical use, and accelerate the time from biomedical advance to beneficial therapy, often referred to as the bench-to-bedside process.

“Most research in this field focuses on the purity of generated cell populations; the efficiency of differentiation goes unreported,” concluded Dr Ungrin. “However our research provides an important template for future studies of pluripotent stem cells, particularly where cells will need to be produced in quantity for medical or industrial uses.”

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Courtesy: Wiley-Blackwell

Plant seeds protect their genetic material against dehydration

by Biomechanism                                                                                                                                   Plant seeds represent a special biological system: They remain in a dormant state with a significantly reduced metabolism and are thus able to withstand harsh environmental conditions for extended periods. The water content of maturing seeds is lower than ten percent.

Researchers from the Max Planck Institute for Plant Breeding Research in Cologne have now discovered that the genetic material in seeds becomes more compact and the nuclei of the seed cells contract when the seeds begin to mature. The seeds probably protect their genetic material against dehydration in this way.

Cell nucleus of a plant seed in a dormant state (left) and after germination (right). The DNA in the smaller nucleus (blue) is more tightly compacted than in the larger one (green: methylated DNA). Photo: © MPI for Plant Breeding Research

Plants prepare for changing environmental conditions in the best possible way by developing dormant seeds. Seeds that mature in autumn, for example, have no problem surviving the harsh conditions of winter. And when the seeds encounter more pleasant external conditions in spring, they germinate and reboot their metabolism, which has been running at a low speed. In archaeological excavations, seeds have even been found that had survived for several thousand years and were still able to germinate.

Dry seeds represent a transitional stage between embryonic and seedling stages. During developmental transitions, the genes that control the new state must be activated while the genes for the “old” stage are silenced. The genes in the cell nucleus are surrounded by proteins. This complex – the chromatin – can be tightly or loosely packed. The degree of compactness of the chromatin regulates the activity of the genes: the more “open” the chromatin, the better the genes can be read.

It was not known up to now whether the reduced metabolic activity or low water content of seeds was linked with changes in the chromatin. The research team working with Wim Soppe from the Max Planck Institute for Plant Breeding Research has now shown in studies on the thale cress that the cell nuclei clearly contract during seed maturation and the chromatin compacts as part of this process. Both processes are reversed during germination. “The size of the nucleus is independent of the state of dormancy of Arabidopsis thaliana seeds,” says Soppe. Instead, the reduction of the nucleus is an active process, the function of which is to increase resistance to dehydration. Again, the condensation of the chromatin arises independently of the changes in the nucleus.

Thanks to the discoveries of the Cologne-based researchers it may be possible to protect other organisms against dehydration, as the mechanisms that regulate the organisation of the chromatin have undergone little or no change over the course of evolution.

________

Swiss scientists prove durability of quantum network

by Biomechanism                                                                                  

Scientists and engineers have proven the worth of quantum cryptography in telecommunication networks by demonstrating its long-term effectiveness in a real-time network.

Their international network, created in collaboration with ID Quantique and installed in the Geneva metropolitan area and crossing over to the site of CERN in France, ran for more than one-and-a-half years from the end of March 2009 to the beginning of January 2011.

Published on 2nd of December, in the Institute of Physics and German Physical Society’s New Journal of Physics, the researchers’ study documents the longest ever deployment of a quantum key distribution (QKD) network and demonstrates its robustness and reliability when coupled with a real-time telecommunications network.

Cryptography—the practice of protecting information from third parties—has long been achieved by encrypting data with a set of complex mathematical algorithms; however, with the power of computers continuing to increase, it is becoming harder to make these algorithms watertight.

Physics has rather conveniently come up with a solution to this ever-growing problem through a process known as quantum key distribution (QKD). QKD is a process that enables two parties to share a secret key before using that key to protect data they want to send over a network.

The key that the two parties share is built up from a stream of photons—the basic unit of light. In a theoretical scenario where Alice and Bob want to protect a piece of information with a quantum key, Alice would send a stream of photons to Bob with each one having a specific orientation, called polarisation: photons can ‘spin’ vertically, horizontally and diagonally.

Bob would then attempt to measure the photons coming in by randomly choosing which direction to measure them in. Sometimes he will choose the correct orientation, other times he won’t. Alice and Bob would then share the measurements using classical communication methods, simply stating if Bob was right or wrong, but not mentioning the actual direction the photons were spinning in.

Alice can then discard all of Bob’s wrong measurements and use the correct ones to encrypt their secret data. The beauty of QKD is that if a potential eavesdropper wanted to get hold of this key, they would actually destroy the photons when trying to measure them. As a result, they would need to send their own stream of photons on to Bob to cover their tracks, but this would introduce errors and be discarded during key distillation.

QKD is not a new phenomenon and has already been used for a number of applications: notably by ID Quantique to protect the votes in Geneva’s elections and in other commercial installations where high security is needed.

For QKD to become more widespread in the commercial world, its reliability needed to be thoroughly tested as these networks run constantly all year round. Furthermore, the robustness of the network needed to be demonstrated as the systems are being taken out of safeguarded laboratories and placed into more demanding environments.

Co-author of the study Dr Damien Stucki said: “This experiment is a big step in the direction of a wider deployment of QKD in telecommunications networks. From a scientific point of view, the deployment of the quantum layer over a duration of 21 months with high reliability is very significant.

“The SwissQuantum network was very reliable, with the only interruptions coming from external problems, such as power cuts and air conditioning problems, not the QKD layer.”

The chimpanzee who sees sounds

Apes' association of tones and shades may hold clues to human synaesthesia and language.

Ewen Callaway

Chimpanzees meld sounds and colours, associating light objects with high tones and dark objects with deeper tones.

The finding hints that chimps, like humans, experience some form of synaesthesia, an uncommon condition in which the senses become intertwined, says Vera Ludwig, a cognitive neuroscientist at Charité Medical University in Berlin, Germany, who led a study published this week in Proceedings of the National Academy of Sciences¹

. Some synaesthetes associate different colours with letters and numbers, for instance, whereas others taste shapes.

Chimpanzees, like humans, seem to associate high-pitched tones with light colours and low-pitched ones with dark colours.

Gravity Giant Productions / Getty Images

Nearly all humans tend to link high-pitched sounds with lighter, brighter hues and bass-filled sounds with dark shades. People judge high vowels, such as 'mil', as white, for example, and consider lower-toned syllables, such as 'mol', as black. Ludwig thinks such connections represent a mild form of synaesthesia, with both emerging from neural cross-wiring between nearby brain regions involved in processing senses.

To determine whether humans learn to associate sounds and colours from others, or whether they are innate and do not require language, Ludwig searched for the associations in captive chimpanzees.

She and colleagues at Kyoto University in Japan showed six chimps aged 8 to 32 a small black or white box, and then trained them to to select a square of the same colour on a screen to receive a fruit reward. The apes also heard a high or low tone when making their choice.

When high tones accompanied white squares and low tones were matched with black, the animals picked the correct colour 93% of the time, on average. When the colours and sounds were reversed, their success rate fell to about 90%.

White noise

In the same game, 33 humans made too few mistakes to detect any perceptual bias. But humans did make correct decisions more quickly when sounds and colours matched.

Because chimps and humans showed similar biases to paired tones and colours, language is not needed to perceive the links, Ludwig says. She suggests instead that these biases were present in the common ancestor of both species, which lived approximately six million years ago, and may have influenced human language.

Edward Hubbard, a neuroscientist at Vanderbilt University in Nashville, Tennessee, who has studied the neural basis of synaesthesia, doubts that chimps experience the same range of synaesthesetic experiences as humans. The human condition involves words, numbers and other cultural constructs, he points out.

“There may be other forms of synesthesia, such as seeing colours for sounds, or hearing sounds in response to visual motion, that are present in non-human animals,” says Hubbard.

However, Danko Nikolic, at the Max Planck Institute for Brain Research in Frankfurt, Germany, questions whether study has any relationship to synaesthesia. He distinguishes perceptual quirks such as the sound-colour correspondence from true synaesthesia, which he believes emerges from associations between higher concepts, not crossed connections in brain areas that process senses. “Too many phenomena have been named synaesthesia,” he says.

Finding synaesthesia in chimpanzees, or any other animal, could prove difficult, given the rarity of the phenomenon in humans and the subjective nature of the experience, Ludwig says. Estimates vary hugely, but one study estimated that about one percent of people see numbers or letters as having colour²

. Her Japanese colleagues are instead looking for other examples in which one sense influences the perception of another in chimps. Humans also associate low pitches with large objects, for instance.

Nature

doi :10.1038/nature.2011.9541

References

1. Ludwig, V., Adachi, I. & Masuzawa, T. Proc. Natl. Acad. Sci. USA http://dx.doi.org/10.1073/pnas.112605108
    (2011).
   Show context
2. Simner, J., Mulvenna, C., Sagiv, N., Tsakanikos, E., Witherby, S. A., Fraser, C., Scott, K. & Ward, J. Perception 35, 1024–1033 (2006).

Source: Nature
http://www.nature.com/news/the-chimpanzee-who-sees-sounds-1.9541?WT.ec_id=NEWS-20111206

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Study identifies mechanisms cells use to remove bits of RNA from DNA strands

by Biomechanism 

When RNA component units called ribonucleotides become embedded in genomic DNA, which contains the complete genetic data for an organism, they can cause problems for cells. It is known that ribonucleotides in DNA can potentially distort the DNA double helix, resulting in genomic instability and altered DNA metabolism, but not much is known about the fate of these ribonucleotides.

Georgia Tech School of Biology graduate student Ying Shen, assistant professor Francesca Storici and graduate student Kyung Duk Koh (left-right) discuss their recent study results, which provide a mechanistic explanation of how ribonucleotides embedded in genomic DNA are recognized and removed from cells. Credit: Georgia Tech/Gary Meek

A new study provides a mechanistic explanation of how ribonucleotides embedded in genomic DNA are recognized and removed from cells. Two mechanisms, enzymes called ribonucleases (RNases) H and the DNA mismatch repair system, appear to interplay to root out the RNA components.

“We believe this is the first study to show that cells utilize independent repair pathways to remove mispaired ribonucleotides embedded in chromosomal DNA, which can be sources of genetic modification if not removed,” said Francesca Storici, an assistant professor in the School of Biology at the Georgia Institute of Technology. “The results also highlight a novel case of genetic redundancy, where the mismatch repair system and RNase H mechanisms compete with each other to remove misincorporated ribonucleotides and restore DNA integrity.”

The findings were reported Dec. 4, 2011 in the advance online publication of the journal Nature Structural & Molecular Biology. The research was supported by the Georgia Cancer Coalition, National Science Foundation and Georgia Tech Integrative BioSystems Institute.

Storici and Georgia Tech biology graduate students Ying Shen and Kyung Duk Koh conducted the study in collaboration with Bernard Weiss, a professor emeritus in the Department of Pathology and Laboratory Medicine at Emory University.

“We wanted to understand how cells of the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae tolerate the presence of different ribonucleotides embedded in their genomic DNA. We found that the structure of a ribonucleotide tract embedded in DNA influenced its ability to cause genetic mutations more than the tract’s length,” said Storici.

With double-stranded DNA, when wrong bases are paired or one or few nucleotides are in excess or missing on one of the strands, a mismatch is generated. If mismatches are not corrected, they can lead to mutations.

The researchers found that single mismatched ribonucleotides in chromosomal DNA were removed by either the mismatch repair system or RNase H type 2. Mismatched ribonucleotides in the middle of at least four other ribonucleotides required RNase H type 1 for removal.

“We were excited to find that a DNA repair mechanism like mismatch repair was activated by RNA/DNA mismatches and could remove ribonucleotides embedded in chromosomal DNA,” explained Storici. “In future studies, we plan to test whether other DNA repair mechanisms, such as nucleotide-excision repair and base-excision repair, can also locate and remove ribonucleotides in DNA.”

Using gene correction assays driven by short nucleic acid polymers called oligonucleotides, the researchers showed that when ribonucleotides embedded in DNA were not removed, they served as templates for DNA synthesis and produced a mutation in the DNA. If both the mismatch repair system and RNase H repair mechanisms are disabled, ribonucleotide-driven gene modification increased by a factor of 47 in the yeast and 77,000 in the bacterium.

Defects in the mismatch repair system are known to predispose a person to certain types of cancer. Because the mismatch repair system is conserved from unicellular to multicellular organisms, such as humans, this study’s findings open up the possibility that defects in the mismatch repair system could have consequences more critical than previously thought given the newly identified function of mismatch repair to target RNA/DNA mispairs.

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The results also provide new information on the capacity of RNA to play an active role in DNA editing and remodeling, which could be the basis of an unexplored process of RNA-driven DNA evolution.

This project was supported by the National Science Foundation (NSF) (Award No. MCB-1021763). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NSF.