Cancer Research UK scientists, including Professor Steve Jackson of the University of Cambridge, believe they have discovered the final piece of the picture of how cells fix a severe type of DNA damage thereby reducing the chances that the cells become cancerous. Their findings are in the latest issue of the journal Cell.

Prof Jackson discovered the first component of one particular DNA repair process over ten years ago. More pieces were found, and eventually scientists thought they had the whole process mapped out. But recent evidence came to light that suggested there was still one bit missing. Now Prof Jackson has finished what he started by discovering a new molecule that completes the picture.

The molecule is called XLF and while it may have a role in causing cancer, it can possibly also be targeted by new cancer treatments – for example, blocking the action of XLF in cancer cells could ‘soften up’ the cells and allow radiotherapy to deliver more easily a knockout blow.

Prof Jackson said: “You could say we went fishing. We know molecules in these processes tend to bind together in order to work, so Peter Ahnesorg – a PhD student in my laboratory – used an established component of the repair pathway as bait and cast it into a sea of proteins. Then he pulled out the bait and examined what was stuck to it.

“As well as catching the usual debris and old boots, we had what looked like a real fish, a molecule that hadn’t ever been studied before. And now we’ve confirmed it is, in fact, the missing part of this jigsaw.”

Professor John Toy, medical director at Cancer Research UK, said: “Cells have a number of complicated processes to repair damaged DNA. This is necessary in protecting cells from the kinds of mutations that sometimes cause them to become cancerous. Researching DNA repair helps us enormously to gain a better understanding of why people get cancer.

“We hope to exploit these processes in cancer treatment. Most types of chemotherapy and radiotherapy work by causing such damage in cancer cells. The XLF molecule may complete our understanding of this DNA repair process, and the new knowledge about this protein can hopefully be used to improve cancer therapy.”


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