Grant: Operating Grant

Tumour suppressors are genes that prevent cells from becoming cancerous by controlling their growth and division. We have identified a novel tumour suppressor called Hace1 in a type of childhood kidney cancer, but have since found that loss of Hace1 function (e.g. through mutation or deletion of the Hace1 gene) can cause many different kinds of cancer. We believe that Hace1 mediates its protective effects via regulation of the cell's response to oxidative stress; when oxidants (which can damage the exposed, vulnerable DNA that is present in dividing cells) are detected, Hace1 kickstarts a process that prevents the cell from dividing. Loss of Hace1 therefore sensitizes cells to DNA damage, which in turn can create cancer-causing mutations in other genes. In this project, we propose to find out exactly how Hace1 responds to oxidative stress, by identifying which proteins it binds to and regulates. We will also determine whether information about the presence or absence of Hace1 in tumour cells can be used in the clinic - for example, cells that lack Hace1 may be more sensitive to chemotherapy drugs that act by damaging the DNA of cancer cells while leaving normal cells unharmed.