ATM and Cellular Response to DNA Damage

Most human cancers display a myriad of genetic changes, a characteristic often attributed to genome instability. Cytogenetic studies have long identified chromosomal aberrations as a hallmark of human tumours, but the causes and consequences of genomic defects in tumours still remain to be fully understood. In particular, the role of genome instability in the development of human cancers as well as its relevance to treatment paradigms continue to evoke intense debate. To address these critical issues it is clearly important to understand the mechanisms that give rise to genome instability. This book reviews both genetic and biochemical data on the origin of genome instability and its impact on carcinogenesis. Reflecting recent discoveries and ongoing research, it discusses DNA repair mechanisms and hereditary cancer syndromes, as well as checkpoint mechanisms operating to safeguard chromosome integrity during cell cycle progression. Moreover, it summarises our current understanding of the various defects that may allow cancer cells to rapidly accumulate critical mutations and evolve, through processes reminiscent of Darwinian selection, an increasingly aggressive behaviour. Hopefully, this book will stimulate thought, discussion and experimentation, and serve as a rich source of information for a wide audience, including advanced students, researchers and clinical oncologists.