Clastogenic and aneugenic DNA damage in HTLV-1 Tax-expressing cells

The probability of developing cancer increases with advancing age. Presentation of cancer is the net outcome between processes which generate abnormal cells and those which eliminate them. It has been estimated that the number of sporadic genetic changes needed to convert a normal to a malignant cell are so numerous that one might not mathematically expect cancers to emerge during a human lifespan. However, the fact that cancers are commonly seen suggests that cells are not simply subject to ambient mistakes. Indeed, it is now clear that in many cases cells show an accelerated proclivity for genetic mutations after the acquisition of a "mutator" phenotype. Such mutator phenotype could either arise spontaneously or be induced after infection with an oncogenic virus such as human T cell leukemia virus type I (HTLV-I). In this chapter, we explore the evidence supporting the notion that HTLV-I Tax functions early in ATL-transformation by conferring a imitator phenotype to cells. We review how Tax affects cellular genetic stability by dysregulation of the mitotic spindle assembly checkpoint and other repair pathways to produce aneuploidy and clastogenic DNA damage.