-With pictures-
A new study has deciphered the mechanical code of DNA to reveal previously unknown ways in which nature encodes biological information in DNA sequence.
Led by Durham University, UK, an international team of researchers used a next-generation DNA-sequencing based technology called loop-seq, which they had 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, i.e., the mapping between local sequence and the local deformability of DNA.
Additionally, 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. Abberant methylation has been linked to several cancers.
The discovery that methylation alters the mechanical code presents the possibility that biological development programmes, or diseases such as cancer, could be achieving a part of their effects on cells by altering the information encoded via the mechanical code.
The research was carried out along with colleagues from Johns Hopkins University, USA, Barcelona Institute of Science and Technology, Spain, and the University of Barcelona, Spain. It has been published in the journal Nature Structural & Molecular Biology.
Lead author of the study, Dr Aakash Basu of Durham University, said: “DNA is a book containing instructions that cells need to survive. 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.”
They point out that 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 provide 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.
The researchers expect this knowledge to guide future therapeutic and bioengineering developments.
ENDS
Media Information
Dr Aakash Basu is available for interview and can be contacted on [email protected]
Alternatively, please contact Durham University Communications Office for interview requests on [email protected]
Source
“Deciphering the mechanical code of the genome and epigenome”, (2022), A Basu, D Bobrovnikov, B Cleza, J Arcon, Z Qureshi, M Orozco and T Ha, Nature Structural & Molecular Biology.
An embargoed copy of the paper is available from Durham University Communications Office. Please email [email protected]
Full paper can be accessed here after the embargo lifts: www.doi.org/10.1038/s41594-022-00877-6
Graphics
Associated images are available via the following link: https://www.dropbox.com/scl/fo/2v9gmxhzjuaqs5goqoi1o/h?dl=0&rlkey=9uwfvvlch0a8vk06looixkbm8
Useful Web Links
Dr Aakash Basu staff profile: https://www.durham.ac.uk/staff/aakash-basu/
Department of Biosciences: https://www.durham.ac.uk/biological.sciences/
Biomolecular Interactions group: https://www.durham.ac.uk/departments/academic/biosciences/research/groups/biomolecular-interactions/
About Durham University
Durham University is a globally outstanding centre of teaching and research based in historic Durham City in the UK.
We are a collegiate university committed to inspiring our people to do outstanding things at Durham and in the world.
We conduct boundary-breaking research that improves lives globally and we are ranked as a world top 100 university with an international reputation in research and education (QS World University Rankings 2023).
We are a member of the Russell Group of leading research-intensive UK universities and we are consistently ranked as a top 10 university in national league tables (Times and Sunday Times Good University Guide, Guardian University Guide and The Complete University Guide).
For more information about Durham University visit: www.durham.ac.uk/about/
END OF MEDIA RELEASE – issued by Durham University Communications Office.
Journal
Nature Structural & Molecular Biology
DOI
10.1038/s41594-022-00877-6