![]() CDA is often overexpressed in certain tumour types, including pancreatic cancer.Įxploiting the unexpected killing of cancer cells by epigenetically modified nucleotides, Kriaucionis and his team demonstrated in a model system that modified Cs can be used as a specific anti-cancer agent. ![]() It was the cancer cell lines that expressed unusually high levels of a protein called cytidine deaminase (CDA) that made this mistake in recycling. They don’t use the modified nucleosides, so the new DNA is epigenetically 'clean.' However, when they looked at the recycling process in cancer cell lines, the researchers discovered that some of the cancer cells are able to transform these nucleosides, allowing incorporation into new DNA. The puzzle that Kriaucionis and his colleagues set out to unravel was how cells prevent recycled and chemically modified 'Cs' from ending up in the wrong places in new DNA.Ĭrucially, they found that the enzymes that recycle nucleotides are highly specific. If the epigenetic modifications are on the wrong C nucleotides, they could make cells cancerous or kill them. These chemical modifications, which are called 'epigenetic' changes, are important for controlling genes and need to be in the correct places in DNA for cells to function normally. However, one of the four types of nucleotides in DNA-the 'C' in genetic sequences-is often chemically modified. In addition to making new nucleotides, they recycle chemical parts from the DNA of dying cells, or DNA that we ingest in our diets. 'We were excited that our biochemical analysis uncovered 'loopholes,' which we hope can be exploited for intervention in cancer.'Ĭells are thrifty when it comes to synthesizing new DNA. In the current study, our research group sought to find out what happens to these modified bases when DNA is recycled,' says Skirmantas Kriaucionis, lead author and assistant member of the Ludwig Institute for Cancer Research, Oxford. 'In the past few years we and others discovered a new set of biological DNA modifications.
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