Abl-Bcr

When the chimeric gene is created as a result of a double stranded break in the DNA, it produces a chimeric protein. In the case of the Abl-Bcr chimeric gene, this lead to an overactive kinase and eventually cancer. Bcr replaces the N-terminal portion of the Abl protein, which in the wild type Abl is responsible for inactivating Abl at the right time. In addition, the CAP domain of the Abl and the myristate are not present on the chimeric Bcr-Abl gene, which normally keep Abl in the inactive state. Since Abl is normally involved in DNA damage response, regulation, and cell motility, when the chimeric form is present all of these processes are affected. Bcr-Abl does not have the ability to enter the nucleus, affecting its DNA damage response, and is hyperactive. Bcr-Abl is able to signal through additional pathways as well, including proliferative pathways. This eventually leads to CML.