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How Strange Twists in DNA Orchestrate Life
DNA is probably best known for its iconic shape—the double helix that James Watson and Francis Crick first described more than 60 years ago. But the molecule rarely takes that form in living cells. Instead, double-helix DNA is further wrapped into complex shapes that can play a profound role in how it interacts with other molecules. “DNA is way more active in its own regulation than we thought,” said Lynn Zechiedrich, a biophysicist at Baylor College of Medicine and one of the researchers leading the study of so-called supercoiled DNA. “It’s not a passive [molecule] waiting to be latched on to by proteins.”
Zechiedrich’s newest findings, published in Nature Communications in October, capture the dynamic nature of supercoiled DNA and point to what could be a new solution to one of DNA’s longstanding puzzles. The letters of the genetic code, known as bases, lie hidden within the helix—so how does the molecular machinery that reads that code and replicates DNA get access? Specialized proteins can unzip small segments of the molecule when it’s replicated and when it’s converted into RNA, a process known as transcription. But Zechiedrich’s work illustrates how DNA opens on its own. Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Additional work by David Levens, a biologist at the National Cancer Institute, has shown that transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read.
...
For three decades, most scientists assumed that supercoiling probably wasn’t very important in complex cells, which have special enzymes that snip and untangle knotted DNA. These enzymes help prevent the buildup of troublesome stress. But they aren’t 100 percent effective. In 2008, Levens, the National Cancer Institute biologist, led a team that detected supercoils in human cells, reigniting interest in DNA’s higher-order structure.
Levens and collaborators found that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself effects how the molecule responds to supercoiling. For example, the researchers identified a specific sequence of DNA that’s prone to opening when stressed, like a weak spot in an old inner tube. The segment acts as a sort of chemical cruise control; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA.
Levens says these structural changes also help DNA communicate along its length. Just as pressing an inner tube makes a weak spot bulge, changes in the shape of one part of the DNA molecule might trigger stress elsewhere along its length, which in turn might help regulate genes.
http://www.scientificamerican.com/article/how-strange-twists-in-dna-orchestrate-life/
Zechiedrich’s newest findings, published in Nature Communications in October, capture the dynamic nature of supercoiled DNA and point to what could be a new solution to one of DNA’s longstanding puzzles. The letters of the genetic code, known as bases, lie hidden within the helix—so how does the molecular machinery that reads that code and replicates DNA get access? Specialized proteins can unzip small segments of the molecule when it’s replicated and when it’s converted into RNA, a process known as transcription. But Zechiedrich’s work illustrates how DNA opens on its own. Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Additional work by David Levens, a biologist at the National Cancer Institute, has shown that transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read.
...
For three decades, most scientists assumed that supercoiling probably wasn’t very important in complex cells, which have special enzymes that snip and untangle knotted DNA. These enzymes help prevent the buildup of troublesome stress. But they aren’t 100 percent effective. In 2008, Levens, the National Cancer Institute biologist, led a team that detected supercoils in human cells, reigniting interest in DNA’s higher-order structure.
Levens and collaborators found that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself effects how the molecule responds to supercoiling. For example, the researchers identified a specific sequence of DNA that’s prone to opening when stressed, like a weak spot in an old inner tube. The segment acts as a sort of chemical cruise control; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA.
Levens says these structural changes also help DNA communicate along its length. Just as pressing an inner tube makes a weak spot bulge, changes in the shape of one part of the DNA molecule might trigger stress elsewhere along its length, which in turn might help regulate genes.
http://www.scientificamerican.com/article/how-strange-twists-in-dna-orchestrate-life/