New Zealand scientists have unraveled the 3D structure of two proteins that control DNA packaging, BAP1 and ASXL1, potentially explaining why some people may be at risk of developing specific cancers. The University of Otago team published its findings yesterday in Nature Communications.
DNA is normally wrapped around proteins and packaged for efficient storage and to control which genes are active. Many proteins help to manage this packaging process and when it is disrupted, cancer can occur. According to Peter Mace, from the department of biochemistry, mutations in these proteins occur in many different cancers including melanomas, mesothelioma, renal cancers, and leukemia. BAP1 mutations are particularly common in mesothelioma.
The new structure helps to explain how the two proteins co-operate to remove DNA-packaging markers in normal cells and how their function is disrupted in tumors.
This is the first structure of these proteins to be captured, which the researchers achieved by working on fruit fly versions of the proteins that have the same important parts as the human proteins, but are slightly less complicated. "This is the best model we currently have for how the human proteins work," Dr Mace explains.