The NEIL3 enzyme has long been known to repair ‘day-to-day’ oxidative damage to DNA that is implicated in diseases of ageing, including dementia and cancer.

But evidence that NEIL3 is also helping cancer cells survive certain types of chemotherapy has been described in a paper in Scientific Reports, published on Tuesday, December 12.

It does so by allowing cancer cells to unhook so-called cross links which prevent the DNA from replicating before cell division. Under normal circumstances this decoupling causes irreparable damage killing the cell entirely, but apparently not in the presence of NEIL3.

“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,” explains Dr Rhoderick Elder, of the University of Salford.

“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,” he said.

Using synthetic DNA in the laboratory, Dr Elder and collaborators at the University of Liverpool and Université Paris-Sud, obtained experimental data that showed how NEIL3 was correcting these DNA cross links. Based on this data, they suggested a novel model of how NEIL3 can bypass these complex knots in the DNA without generating highly toxic intermediates.

The study could have implications for the application of certain types of chemotherapy which induce cross links to preclude cell division and tumour growth.

“If we can inhibit NEIL3, it could potentially remove a barrier to the effectiveness of certain treatments,” added Dr Elder.

Further research is now underway to knock out NEIL3 using CRISPR-Cas9 gene editing to examine the effect of a lack of NEIL3 on the sensitivity of human cancer cells to certain chemotherapeutic agents.

More information at https://www.alphagalileo.org

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