Wei Hung (William) Kuo

2005 Research Trainee Award, Junior Graduate Studentship

ING1b promotes chromatin relaxation for nucleotide excision repair of UV induced DNA lesions|,|

In mammalian cells, DNA is packaged into a tight structure called chromatin. The DNA in cells can be damaged by a number of agents, including ultraviolet light, and failure to repair damaged DNA can lead to genetic mutations that can kill cells or induce cancer formation. In order for core DNA-repair proteins to access damaged genetic material, the condensed chromatin structure must be relaxed. The protein ING1b (a growth inhibitor) is known to enhance the repair of DNA in ultraviolet-injured cells by relaxing the chromatin structure. Conversely, mutations in the ING1b gene within a region called the PHD finger have been shown to reduce DNA repair and have also been correlated with reduced survival of patients with melanoma (an aggressive form of skin cancer). Building on the research findings of his supervisor, Dr. Gang Li, William Kuo is studying the mechanisms through which ING1b assists DNA repair. He hypothesizes that ING1b associates with a class of chromatin-modifying protein complexes, called histone acetyl transferase (HAT) to induce chromatin relaxation. He will also explore the possibility that the PHD finger tethers the ING1b-HAT complex to chromatin for its relaxation during DNA repair. He hopes that an understanding of these mechanisms could lead to the development of new therapies for cancers caused by damage to DNA. Completed award term, June 2006

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