How Strange Twists in DNA Orchestrate Life

Emily Singer in Quanta:

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 furtherwrapped 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,” saidLynn 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.

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.”

More here.