Structure and RNA-cleaving function of apurinic/apyrimidinic endonuclease 1 (APE1)

Cancer occurs when cells won’t stop growing. The source of this malfunction is often an alteration in DNA, the genetic instructions for making different proteins inside a cell. To make proteins, a gene is copied out from the DNA into a molecule called mRNA. The mRNA travels out of the cell nucleus and into the cytoplasm, where its genetic instructions are used as a template for synthesizing proteins. C-myc mRNA serves as a template for synthesizing the c-Myc protein. This protein plays fundamental roles in regulating growth, differentiation, and cell death in virtually all mammalian cells, and it is implicated in diverse human cancers. In fact, it has been estimated that c-Myc dysfunction contributes to one-seventh of all cancer deaths. One way that cells regulate their level of proteins is by destroying mRNA in the cytoplasm by chemically cutting, or cleaving, its molecular structure. Recently, the enzyme APE1 was discovered to cleave c-myc mRNA. This opens the potential for using APE1 to reduce or eliminate levels of c-Myc protein in the cytoplasm as a potential treatment for cancer. Wan Kim is exploring the function of APE1 as an mRNA destroyer. He is identifying the key amino acids and mechanisms APE1 uses to cleave c-myc mRNA, and determining whether the enzyme cleaves any other types of mRNA. Kim hopes to generate valuable insights into how APE1 can degrade c-myc mRNA and influence gene expression. Also, the study will provide useful information on the potential design of novel approaches in cancer treatment.