Understanding how eukaryotic genome integrity is maintained over generations – during which time the genome has to be accurately duplicated in each cell cycle – is one of the fundamental problems of modern biology. It is also a critical aspect of the more general problem of understanding the mechanisms that control cellular proliferation and prevent oncogenesis. The stability of the genome depends upon the precise operation of the DNA replication machinery and upon the checkpoint mechanism that deals with various perturbations of DNA replication. If undetected by the checkpoint, perturbed replication forks become unstable and may undergo catastrophic collapse, resulting in cell death or mutagenic chromosomal damage. For this reason, defects in the DNA replication checkpoint are known causes of genome instability and cancer.
