A rare DNA base, previously thought to be a temporary modification, has been shown to be stable in mammalian DNA, suggesting that it plays a key role in cellular function.
Researchers from the University of Cambridge and the Babraham Institute have found that a naturally occurring modified DNA base appears to be stably incorporated in the DNA of many mammalian tissues, possibly representing an expansion of the functional DNA alphabet.
The new study, published in the journal Nature Chemical Biology, has found that this rare ‘extra’ base, known as 5-formylcytosine (5fC) is stable in living mouse tissues. While its exact function is yet to be determined, 5fC’s physical position in the genome makes it likely that it plays a key role in gene activity.
“This modification to DNA is found in very specific positions in the genome – the places which regulate genes,” said the paper’s lead author Dr Martin Bachman, who conducted the research while at Cambridge’s Department of Chemistry. “In addition, it’s been found in every tissue in the body – albeit in very low levels.”
“If 5fC is present in the DNA of all tissues, it is probably there for a reason,” said Professor Shankar Balasubramanian of the Department of Chemistry and the Cancer Research UK Cambridge Institute, who led the research. “It had been thought this modification was solely a short-lived intermediate, but the fact that we’ve demonstrated it can be stable in living tissue shows that it could regulate gene expression and potentially signal other events in cells.”
Since the structure of DNA was discovered more than 60 years ago, it’s been known that there are four DNA bases: G, C, A and T (Guanine, Cytosine, Adenine and Thymine). The way these bases are ordered determines the makeup of the genome. In addition to G, C, A and T, there are also small chemical modifications, or epigenetic marks, which affect how the DNA sequence is interpreted and control how certain genes are switched on or off. The study of these marks and how they affect gene activity is known as epigenetics.
5fC is one of these marks, and is formed when enzymes called TET enzymes add oxygen to methylated DNA – a DNA molecule with smaller molecules of methyl attached to the cytosine base. First discovered in 2011, it had been thought that 5fC was a ‘transitional’ state of the cytosine base which was then being removed from DNA by dedicated repair enzymes. However, this new research has found that 5fC can actually be stable in living tissue, making it likely that it plays a key role in the genome.
Using high-resolution mass spectrometry, the researchers examined levels of 5fC in living adult and embryonic mouse tissues, as well as in mouse embryonic stem cells – the body’s master cells which can become almost any cell type in the body.
They found that 5fC is present in all tissues, but is very rare, making it difficult to detect. Even in the brain, where it is most common, 5fC is only present at around 10 parts per million or less. In other tissues throughout the body, it is present at between one and five parts per million.
The researchers applied a method consisting of feeding cells and living mice with an amino acid called L-methionine, enriched for naturally occurring stable isotopes of carbon and hydrogen, and measuring the uptake of these isotopes to 5fC in DNA. The lack of uptake in the non-dividing adult brain tissue pointed to the fact that 5fC can be a stable modification: if it was a transient molecule, this uptake of isotopes would be high.
The researchers believe that 5fC might alter the way DNA is recognised by proteins. “Unmodified DNA interacts with a specific set of proteins, and the presence of 5fC could change these interactions either directly or indirectly by changing the shape of the DNA duplex,” said Bachman. “A different shape means that a DNA molecule could then attract different proteins and transcription factors, which could in turn change the way that genes are expressed.”
CALGARY, Alberta (Reuters) - A wildfire raging in northeastern Alberta near two major oil sands projects nearly doubled in size to 17,000 hectares (42,000 acres) on Wednesday, although firefighters made
If we can't plead stupidity, what else is there? How do we live with ourselves? Is it all the stuff we buy that manages to numb our brains and consciences?
When I see a headline like this one at Bloomberg today, World Needs Record Saudi Oil Supply as OPEC Convenes, there’s just one thought that pops into my head: what the world needs is for us to stop doing this thing we’re doing. Even apart from peak oil concerns, it’s obvious we’re going to run out at some point or another, and it doesn’t matter whether that’s tomorrow or at some other point in the future, though we do know it’s not going to take another 100 years, or even 50.
And nothing will ever take the place of oil; once those unique carbons are gone, that’s it, we’ll have to find a completely different way of running our societies, and if we’re not smart enough to prepare for that beforehand, we’ll be cats fighting in a sack and use the last scraps to kill off each other. And our legacy won’t be the Greek thinkers and Picasso and Dostoyevsky and Walt Whitman and Maria Callas, since there won’t be the means for our children anymore to share what makes man great between them. Our main legacy will instead be bloodshed, we will have gone the exact same path that any non-thinking or even primitive organism would have taken, who don’t have opera or philosophy or poetry to their name.
The number of new cases of cancer in the world is rising, according to a new report that looked at cancer in 118 countries. Globally, the number of new cancer cases increased from 8.5 million in 1990 to 14.9 million in 2013, the study found. The world population rose from 5.3 billion to 7.1 billion during that time. In addition, cancer is accounting for an increasingly greater proportion of deaths: In 1990, 12 percent of all deaths in the countries studied were due to cancer, but in 2013, it was 15 percent.
The researchers specifically looked at 28 different types of cancer, and found that cases from nearly all of these types of cancer have increased in the last two decades — ranging from a 9 percent increase in cervical cancer cases to a 217 percent increase in prostate cancer cases. The only cancer that decreased during the study period was Hodgkin's lymphoma, which saw a 10 percent decrease in the number of new cases between 1990 and 2013.
The overall rise in cancer cases is partly due to longer life spans, since the risk of cancer increases with age. "With life expectancy increasing globally, the future burden of cancer will likely increase," the researchers said. The growing global population, increases in obesity and poor dietary habits also have contributed to the rise, they said.
Cancer is more common in men than in women, with 1 in 3 men worldwide developing cancer before age 79, compared with 1 in 5 women. The most common cancer overall was cancer of the lungs, trachea or bronchus, with 1.8 million new cases and 1.6 million deaths in 2013, followed by breast cancer and colon cancer. The most common cancer in men was prostate cancer, and the most common cancer in women was breast cancer.
A particularly concerning trend is an increase in cancer cases in developing countries, the researchers said. In 2013, the rates of new cancer cases were higher in developing countries than in developed countries for stomach cancer, liver cancer, esophageal cancer, cervical cancer, mouth cancer, and nose and throat cancer.
NEW DELHI (Reuters) - A heat wave in India has killed more than 1,100 people this week as temperatures soar above 47 Celsius (116.6 Fahrenheit), and doctors' leave has been canceled to help cope with the
Chevron warded off a litany of accusations of environmental damage and corporate malfeasance during its annual meeting Wednesday, and after the event the company said the Richmond refinery will remain a major part of its operations.
Psychedelic drugs including LSD and magic mushrooms are much less harmful than has been claimed, and should be reclassified to make it easier for scientists to research their potential benefits, a leading psychiatrist has said.
Researchers have pinpointed the driest location on Earth in the Atacama Desert, a region in Chile already recognised as the most arid in the world. They have also found evidence of life at the site, a discovery that could have far-reaching implications for the search for life on Mars.
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