Copy errors in DNA repeats increase cancer risk

Repetitive sequences in noncoding DNA may lead to the generation of cancer-causing mutations.

Repetitive noncoding DNA, most of which has no known function, makes up around half of the human genome. It was already known that errors in DNA replication are more likely to occur in these areas, and that accumulation of such mutations can contribute to the development of cancer. However, the mechanism by which these errors occur was unclear.

'We wanted to understand why it seems more difficult for cells to copy repetitive DNA sequences than other parts of the genome,' said lead author Dr Gideon Coster from the Institute of Cancer Research (ICR) in London, where the research took place. '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.'

By studying the process of DNA replication in a test tube, Dr Coster and his colleagues found that repetitive noncoding DNA sequences interfere with the action of the DNA replication machinery.

They observed that the DNA replication machinery was able to unwind the DNA strands that form the double helix structure, but would often only copy one strand, rather than both. This in turn could cause the replication to stall and collapse.

DNA replication errors contribute to 'genomic instability': the tendency to generate increasing numbers of mutations through successive rounds of cell division, a hallmark of most cancers.

Professor Kristian Helin, president of the ICR, said: '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,'.

The study was published in Nature Communications.