Non-coding or ‘junk’ DNA could contribute to the development of certain cancers due to how it disrupts the replication of the genome, scientists have discovered.
A team from The Institute of Cancer Research (ICR), London reconstituted the entire process of DNA replication in a test tube in order to understand it more completely.
The team found that non-coding DNA or repetitive patterns of DNA could disrupt the replication of the genome.
In the study, the team describes how repetitive patterns of DNA are copied during replication and can stall the replication entirely. This increases the risk of errors in DNA which can result in mutations, which can be an early driver of cancer.
Specifically, the team 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 scientists now believe that repetitive DNA sequences could trigger a damage response signal indicating that errors in DNA replication have occurred and require repair. When this happens, the risk of mutations and cancer formation and progression can occur, indicating a link between junk DNA and cancer.
In the 1960s, scientists at the ICR first showed 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.
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, added: “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.”