Scientists have found that non-coding ‘junk’ DNA, far from being harmless and inert, could potentially contribute to the development of cancer.
Their study has shown how non-coding DNA can get in the way of the replication and repair of our genome, potentially allowing mutations to accumulate.
It has been previously found that non-coding or repetitive patterns of DNA – which make up around half of our genome – could disrupt the replication of the genome.
But until now scientists have not understood the underlying mechanism, or how it could contribute to cancer’s development.
In the new study, scientists at The Institute of Cancer Research, London, reconstituted the entire process of DNA replication in a test tube in order to understand it more completely.
The researchers were able to describe how repetitive patterns of DNA are copied during replication and how they are able to stall replication entirely – increasing the risk of errors that can be an early driver of cancer. This vital knowledge may eventually lead to better drugs and treatments.
The researchers believe the work could also help to improve the diagnosis and monitoring of some cancers, such as bowel cancer, where common errors in copying the repetitive sequences of DNA indicate whether cancer is progressing.
The study, published in Nature Communications, was funded by Wellcome and the Royal Society, with additional support from The Institute of Cancer Research (ICR) itself.
Scientists at the ICR – a charity and research institute – found that when the DNA replication machinery encountered repetitive DNA, it was able to unwind the DNA strands, but it sometimes failed to copy the opposite DNA strand. This error could cause replication to stall, resulting in collapse of the replication machinery in a manner similar to that induced by DNA damage.
The findings lead scientists to believe that repetitive DNA sequences could trigger a damage response signal indicating that errors in DNA replication have occurred and require repair.
DNA damage and ensuing genome instability are known to promote cancer formation and progression, so the research strengthens the link between junk DNA and cancer.
It was scientists at the ICR who, in the 1960s, provided the first conclusive evidence that DNA damage is the fundamental cause of cancer. In the early 2000s, ICR researchers then showed that drugs called PARP inhibitors could be genetically targeted against cancers with DNA repair mutations.
Our researchers now hope that improved understanding of DNA replication, and how it can go wrong, might lead to new ways of treating the disease.
Study leader Dr Gideon Coster, Team Leader in Genome Replication at The Institute of Cancer Research, London, said:
“We wanted to understand why it seems more difficult for cells to copy repetitive DNA sequences than other parts of the genome. Our study suggests that so-called junk DNA is actually playing an important and potentially damaging role in cells, by blocking DNA replication and potentially opening the door to cancerous mutations.
“We now believe that repetitive DNA sequences trigger a response that is very similar to the one induced by DNA damage, which we know can lead to cancer. Our study therefore fundamentally advances our understanding of cancer, and I’m hopeful it will help us come up with new treatments in the future.”
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“This study helps to unravel the puzzle of junk DNA – showing how these repetitive sequences can block DNA replication and repair. It’s possible that this mechanism could play a role in the development of cancer as a cause of genetic instability – especially as cancer cells start dividing more quickly and so place the process of DNA replication under more stress.
“Understanding the mechanisms underlying genetic mutation and instability is critical if we are to find innovative new ways to treat cancer that exploit fundamental weaknesses in cancer cells.”
Notes to editors
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The Institute of Cancer Research, London, is one of the world’s most influential cancer research organisations.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
The ICR is a charity and relies on support from partner organisations, funders, and the general public. A member institution of the University of London, it is one of the UK’s leading higher education institutions, placing first for biological sciences and second overall in the definitive REF 2021 rankings of UK university research quality, impact and environment, and provides postgraduate higher education of international distinction.
The ICR’s mission is to make the discoveries that defeat cancer.
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Subject of Research
The mechanism of replication stalling and recovery within repetitive DNA
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