MRC Institute of Genetics & Molecular Medicine
MRC Institute of Genetics & Molecular Medicine

DNA unwinding regulates genes

Research reveals how DNA twisting organises gene architecture and function: February 2020

Helix

The DNA blueprint for all living creatures has to be carefully packaged in a cell. It exists as two DNA strands forming a double helix; a curious property of a helix is that it can be over or under-wound. For a long time we have known this will be important for gene organisation and transcription but until now we haven’t had the tools to investigate it.

Researchers at the MRC Human Genetics Unit, University of Edinburgh and the IFOM Oncology Institute in Milan collaborated to understand how these changes in DNA shape are controlled. By carefully synchronising the growth of yeast cells in culture they mapped patterns of DNA twisting and analysed which proteins were bound to the DNA and how these could change the shape of DNA.

The scientists found that two proteins called Top2 and Hmo1 had an important role in winding and relaxing the supercoils around the boundaries of transcribed genes. Versions of these proteins with impaired function caused the DNA to form incorrect structures and increased the likelihood of DNA damage and mutation. This is also relevant because Top2 is a key target for anti-cancer therapies in humans.

This novel research suggests that maintaining the correct structure of DNA is important to avoid damage to cells and mutations in genes. As such, Top2 and Hmo2 can be considered as important guardians of the genome.

This study highlights how international collaborative research can reveal fundamental new insights into biology that can be translated into new therapies for understanding and treating human disease.

Professor Nick GilbertMRC Human Genetics Unit

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