Cancer remains one of the leading causes of death in the developed world and despite impressive advances in therapeutic modalities, only a small subset of patients are currently cured. The underlying genetic heterogeneity of cancers clearly plays a crucial role in determining both the clinical course of individual pathologies and their responses to standard treatments. Although every tumour is to some extent distinct, there are recurrent features of cancers that can be exploited as therapeutic targets and as prognostic and predictive biomarkers; one such attribute is telomere length. Here we discuss the utility of telomere length evaluation in cancer and describe some of the promise and challenges of bringing this into clinical practice.

Replication failures induced by replication fork barriers (RFBs) or global replication stress generate many of the chromosome rearrangement(CR)observed in humangenomic disorders and cancer. RFBs have multiple causes and cells protect themselves from the consequences of RFBs using three general strategies: preventing expression of RFB activity, stabilising the arrested replisome and, in the case of replisome failure, shielding the fork DNA to allow rebuilding of the replisome. Yeast models provide powerful tools to understand the cellular response to RFBs, delineate pathways that suppress genome instability and define mechanisms by which CRs occur when these fail. Recent progress has identified key features underlying RFBs activity and is beginning to uncover the DNA dynamics that bring about genome instability.

An interplay among experimental studies of protein synthesis, evolutionary theory, and comparisons of DNA sequence data has shed light on the roles of natural selection and genetic drift in `silent¿ DNA evolution.

Evolutionary studies suggest that the limbs of vertebrates and the appendages of arthropods do not share a common origin. However, recent genetic studies show new similarities in their developmental programmes. These similarities might be caused by the independent recruitment of homologous genes for similar functions or by the conservation of an ancestral proximaldistal development programme. This basic programme might have arisen in an ancestral outgrowth and been independently co-opted in vertebrate and arthropod appendages. It has subsequently diverged in both phyla to fine-pattern the limb and to control phylum-specific cellular events. We suggest that although vertebrate limbs and arthropod appendages are not strictly homologous structures they retain remnants of a common ancestral developmental programme.