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The ING1b protein facilitates accessibility to UV-damaged nucleosomal DNA

University of British Columbia

ING1b is the most studied ING-family member protein and perhaps the most ubiquitous and highly expressed. This protein is involved in the regulation of various biological functions ranging from senescence, cell cycle arrest, apoptosis, to DNA repair. ING1b is upregulated by UV irradiation and enhances the removal of bulky nucleic acid photoproducts. We provide evidence that ING1b mediates nucleotide excision repair by facilitating access to damaged nucleosomal DNA. Our data suggest that this enhancement effect precedes the actions of damage recognition factor XPC, implicating a role of ING1b in the global genomic repair pathway. Through immunofluorescent imaging we demonstrate that ING1b does not colocalize with UV-induced DNA lesions and is therefore not part of core repair factors. ING1b also undergoes a nucleoli-nucleoplasm shift and increasingly associates with chromatin upon UV irradiation. Microccocal nuclease digestion of genomic DNA reveals however that ING1b facilitates chromatin relaxation and may allow better access to nucleotide excision repair machinery. ING1b can also alter histone acetylation dynamics upon exposure to UV light. Our preliminary observations suggest that p300 is likely a modulator of this event. More importantly, we found that ING1b facilitates DNA access to nucleotide excision repair factor, XPA, and is therefore important in the early steps of the ’Access, Repair, Restore’ model.

Text

2010-01-16

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http://hdl.handle.net/2429/18330

Experimental Medicine

University of British Columbia

UBCV

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