Genome complexity: DNA in 3D also makes coils (Introduction)

by David Turell , Tuesday, January 12, 2016, 20:18 (3237 days ago) @ David Turell

New research shows DNA making coils to allow itself to open up and create different functions:- http://www.scientificamerican.com/article/how-strange-twists-in-dna-orchestrate-life/?W... 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.-"The research hints at an unstudied language of DNA topology that could direct a host of cellular processes. “It's intriguing that DNA behaves this way, that topology matters in living organisms,” said Craig Benham, a mathematical biologist at the University of California, Davis. “I think that was a surprise to many biologists.”-***-"Zechiedrich and her collaborators have spent the last two decades making small pieces of supercoiled DNA, whose behavior better mimics DNA in the living cell. Essentially, they take a short strand of DNA and twist it—once, twice, three times or more—either with or against the coil. Then they glue the ends together. The end result is a tiny circle of DNA coiled in one direction or another. Zechiedrich, her collaborator and Baylor colleague Jonathan Fogg and others have shown that these twisted coils dance, shimmying through a microscopic ballet. Each molecule can assume a variety of shapes, from simple circles to figure eights, racquets, handcuffs, needles and rods. “Linear DNA is stiff and inflexible,” said De Witt Sumners, a mathematician at Florida State University in Tallahassee. “But when you get it bent into a small circle, the duplex opens up and adopts a large number of interesting shapes—this is completely unexpected.”-***-"The findings align with Harris's models, which show that supercoiling can split the two strands of the helix, rotating the DNA bases that normally lie inside the helix to the outside, a phenomenon known as base flipping. Other simulations show that twisting a bit more flips out additional bases, creating a bubble of inside-out DNA. Zechiedrich theorizes these bubbles might provide trigger points for replication or gene expression. This challenges the standard view, in which proteins latch onto DNA and launch these events. “Who's driving the bus in cellular metabolism?” said Sumners. “It's a very dynamic process—DNA and proteins each influences how the other acts and reacts.'”-Comment: 3-D DNA coiling and uncoiling and forming knots show how fluid and dynamic the living cells are. It helps explain how 23,000+ genes make a human