Decrypting the 'mechanical code' of DNA

An international team of researchers has revealed new ways in which nature encodes biological information in a DNA sequence, with their results published in the journal Nature Structural & Molecular Biology.

Researchers from Johns Hopkins University, Durham University, the University of Barcelona and the Barcelona Institute of Science and Technology used a next-generation DNA sequencing-based technology called loop-seq, which they developed, to show that the local sequence of bases along a region of DNA determines the local bendability of DNA. Via a large number of measurements, coupled with computational analysis and machine learning, they determined the mechanical code, or mapping between local sequence and the local deformability of DNA.

DNA is like a book containing instructions that cells need to survive. It is a special kind of book where the ability to turn or fold a page depends 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.

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 researchers found that the mechanical code of DNA can be modified by ‘methylation’, which is a known chemical modification that DNA bases are routinely subject to at various stages in an organism’s development.

The discovery that methylation alters the mechanical code presents the possibility that biological development programs, or diseases such as cancer, could be partly affecting cells by altering the information encoded via the mechanical code. The discovery could therefore help in the treatment of these diseases.

Image credit: iStock.com/ktsimage

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