Team Uncovers Mechanical Code Behind DNA’s Local Bendability

Research led by UK’s Durham University has deciphered the mechanical code of DNA to reveal previously unknown ways in which nature encodes biological information in DNA sequence. The team also found that this mechanical code can be modified by methylation—the process of chemical modification DNA bases are routinely subject to at various stages in an organism’s development but can lead to cancer if it goes awry. The insights could guide future therapeutic and bioengineering developments.

The international team used a next-generation DNA-sequencing based technology called loop-seq to show that the local sequence of bases along a region of DNA determines the local bendability of DNA. Using a large number of measurements, computational analysis, and machine learning, they determined the mechanical code the local sequence uses to determine local deformability of the DNA.

The subsequent discovery that methylation alters this mechanical code presents the possibility that biological development programs as well as diseases such as cancer could be achieving a part of their effects on cells by altering the information encoded via the mechanical code.

It is well known that, reading, copying, packaging, and repairing the genetic information stored in the sequence of bases (the As, Ts, Gs, and Cs) along DNA routinely involves processes that require local mechanical deformations of DNA. The study provides evidence that in diverse organisms ranging from mammals to bacteria, nature and evolution has taken advantage of the mechanical code to locally control DNA deformability, and thus in turn, control critical biological processes that require mechanical distortions of DNA.

“DNA is a book containing instructions that cells need to survive,” says lead author Dr. Aakash Basu of Durham University. “But it’s a very special kind of book, where your ability to turn a page, repair a tear in the page, or fold a page, depend on the words written on the page. This is because in the book of DNA, those words somehow also control the mechanical properties of the paper.”

The research was carried out along with colleagues from Johns Hopkins University, Barcelona Institute of Science and Technology, and the University of Barcelona. It has been published in Nature Structural & Molecular Biology.