Deleting Oncogenes in Cancer Cells with DNA Strand Slippage

Abstract

Oncogenes are DNA sequences which code for proteins that can cause cancer. Therefore, one way to treat cancer is to disrupt or destroy these genes. Lars Zender and colleagues recently discovered two genes that are the most likely causes of liver cancer (1). Zender claims oncogenes cIAP1 and Yap promote tumor growth, and are overexpressed in liver cancer cells. Garcia-Diaz and coworkers have also found that the slipping of DNA strands during synthesis by DNA polymerase can cause single bases to be deleted (2). Applying conditions for this slippage to the replication of the oncogenes in liver cancer cells will cause base deletion and render the gene unable to encode a protein that promotes tumor growth. The experimental control will be DNA sequences matching the oncogenes that will be treated with DNA polymerase λ due to its high rate of base deletion (2). A second experimental control will be DNA treated with DNA polymerase μ. The negative control will consist of untreated DNA. The crystallization process used by Garcia-Diaz and colleagues to uncover the structure of the polymerase and DNA will be used to determine which DNA bases, if any, are deleted. The oncogene will become unable to promote tumor malignancy if its bases are targeted for deletion.
Background
Zender applied genome analysis to human hepatocellular carcinoma cells, or liver cancer cells, and mouse liver tumors to determine the genes cIAP1 and Yap have cancer-causing properties. cIAP1 prevents the cell from undergoing apoptosis and Yap codes for a protein that contributes to tumor growth and malignancy (1). Michael Overholtzer and coworkers reached similar conclusions about he Yap gene (3). Figure 1 on the previous page is a graph showing tumor growth vs. time when various combinations of oncogenes and controls