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How is DNA repair affected by the way DNA is packaged in the cell?

  • Researcher: Professor Wim Vermeulen
  • Institution: Erasmus MC, Rotterdam, Netherlands
  • Award Amount: £202,102 from 1st September 2015 for 3 years
  • Cancer Type: General Cancer Research
How is DNA repair affected by the way DNA is packaged in the cell?
The instruction book carried by every cell of our body, DNA, is continuously being damaged by outside agents like UV light and waste products produced by our own cells.  If the damage isn’t repaired quickly and thoroughly then it can lead to changes known as mutations.  If mutations accumulate, it can lead to cancer.  Dr Vermeulen studies a type of DNA repair known as ‘nucleotide excision repair’, or NER for short.  “We know NER is important because people who are born without a working NER pathway are more likely to develop cancer, particularly skin cancer” he tells us.  But it isn’t only the proteins directly carrying out NER that are important.  To fit its long strands inside a cell, DNA has to be wound up tightly into chromosomes, like a ball of wool.  This winding affects how easily the NER machinery can get to bits of damaged DNA.   “We are studying proteins that control how tightly DNA is wound ” says Vermeulen “these proteins relax areas of DNA that are damaged, opening the door for NER proteins to enter”.   If these ‘DNA unwinding’ proteins aren’t working properly Dr Vermeulen thinks this will have a big impact on how well NER works, and this is what he will study with his Worldwide Cancer Research grant.  “This type of detailed study is important for understanding what really goes wrong at the roots of cancer” he says.  “We hope the results of this project will point the way towards new treatment targets or new ways to diagnose the disease”. This project is important because: For a long time we have known that the NER machinery protects against cancer, but it has only recently become clear that DNA packaging proteins are involved in this process as well. Therefore, we are very excited that this grant enables us to study the interplay between both cellular machineries and their impact on cancer.
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