by University of Sheffield

TEX264 acts at replication forks. Credit: Nature Communications (2020). DOI: 10.1038/s41467-020-15000-w

A new “toolkit” to repair damaged DNA that can lead to aging, cancer and motor neuron disease (MND) has been discovered by scientists at the Universities of Sheffield and Oxford.

Published in Nature Communications, the research shows that a protein called TEX264, together with other enzymes, is able to recognize and “eat” toxic proteins that can stick to DNA and cause it to become damaged. An accumulation of broken, damaged DNA can cause cellular aging, cancer and neurological diseases such as MND.

Until now, ways of repairing this sort of DNA damage have been poorly understood, but scientists hope to exploit this novel repair toolkit of proteins to protect us from aging, cancer and neurological disease.

The findings could also have implications for chemotherapy, which deliberately causes breaks in DNA when trying to kill cancerous cells. Scientists believe targeting the TEX264 protein may offer a new way to treat cancer.

“Failure to fix DNA breaks in our genome can impact our ability to enjoy a healthy life at an old age, as well as leave us vulnerable to neurological diseases like Motor Neuron Disease (MND). We hope that by understanding how our cells fix DNA breaks, we can help meet some of these challenges, as well as explore new ways of treating cancer in the future,” said Professor Sherif El-Khamisy, Co-Founder and Deputy Director of the Healthy Lifespan Institute at the University of Sheffield.

Professor Kristijan Ramadan from the University of Oxford, who co-led the research, said, “Our finding of TEX264, a protein that forms the specialized machinery to digest toxic proteins from our DNA, significantly changes the current understanding of how cells repair the genome and so protect us from accelerated aging, cancer and neurodegeneration. I believe this discovery has a great potential for cancer therapy in the future and we are already pursuing our research in this direction.”

Professor Ramadan added, “I am very proud of my research team who initially discovered the involvement of TEX264 in DNA repair.”

More information: John Fielden et al, TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts, Nature Communications (2020). DOI: 10.1038/s41467-020-15000-w

Journal information:Nature Communications

Provided by University of Sheffield

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Experts discover toolkit to repair DNA breaks linked to aging, cancer and MND

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