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Researching our internal DNA repair toolkit

  • Researcher: Dr Grant Stewart
  • Institution: University of Birmingham, England
  • Award Amount: £216,052 for 3 years from January 2014
  • Cancer Type: General Cancer Research
Researching our internal DNA repair toolkit
Cancer can be caused by damage to the DNA inside our cells. This damage can be from many things such as UV in sunlight or mistakes when the DNA is being copied. All healthy cells have mechanisms to repair this damage. However, these repair mechanisms can sometimes become faulty, which allows the DNA damage to remain. This damage can contribute to, or even cause, the cells to become cancerous and allow tumours to develop. When a piece of damaged DNA is detected, signals are sent to recruit a vast array of molecules that act as a repair kit. One if these molecules is Ubiquitin. Ubiquitin is special because, amongst other things, when attached to another molecule it can signal for it to be destroyed. To counteract this, molecules called de-ubiquiting enzymes (DUBs) are able to remove the ubiquitin tags and prevent unwanted destruction. Dr Stewart is looking at a specific de-ubiquiting enzyme called USP7. USP7 removes ubiquitin from a DNA repair kit molecule called Rad18 which has a key role in efficient DNA repair. If USP7 is absent or inactive, Rad18 is tagged for destruction by ubiquitin. The subsequent low Rad18 levels can then prevent correct repair of DNA damage. Dr Stewart is using his Worldwide Cancer Research grant to further understand how USP7 can help regulate the levels of Rad18. This work is particularly relevant as new drugs which block the activity of USP7 are being developed as anti-cancer treatments.
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