An anti-ageing enzyme may also help cancer cells survive chemotherapy, British researchers have found.
The NEIL3 enzyme is a type of DNA glycosylase protein, a family of enzymes involved in base excision repair – the mechanism by which damaged bases in DNA are removed and replaced.
It has previously been linked to protection from dementia and cancer because of its ability to repair oxidative damage.
However, experiments by Dr Rhoderick Elder of the University of Salford, UK, and colleagues indicate that NEIL3 can undermine chemotherapy by preventing cell death.
They explain in Scientific Reports yesterday (12 October) that some chemotherapy drugs create cross-links which prevent the DNA from replicating before cell division, leading to cancer cell death. But NEIL3 allows cancer cells to unhook these cross-links, they report.
The team collaborated with researchers at the Universite Paris-Sud, France, to view the effect of NEIL3 on cross-links using synthetic DNA.
Dr Elder says: "The protein appears to be allowing the cancer cells to overcome a problem that might otherwise be terminal for them; so rather than be locked in and die, they can escape, duplicate and the cancer continues to grow. A previous study on mice cells showed that cells are more sensitive to certain types of chemotherapy when NEIL3 is not present, and we were intrigued as to why. If we can inhibit NEIL3, it could potentially remove a barrier to the effectiveness of certain treatments."
They are now working on precise ways of knocking out NEIL3 with gene editing tools.
Martin, P. R. et al. The Human DNA glycosylases NEIL1 and NEIL3 Excise Psoralen-Induced DNA-DNA Cross-Links in a Four-Stranded DNA Structure. Scientific Reports 12 December 2017; doi: 10.1038/s41598-017-17693-4 [abstract]
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