How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

DNA double-strand breaks (DSBs) are a significant threat to the viability of a normal cell, since they can result in loss of genetic material if mitosis or replication is attempted in their presence. Consequently, evolutionary pressure has resulted in multiple pathways and responses to enable DSBs to be repaired efficiently and faithfully. Cancer cells, which are under pressure to gain genomic instability, have a striking ability to avoid the elegant mechanisms by which normal cells maintain genomic stability. Current models suggest that in normal cells DSB repair occurs in a hierarchical manner that promotes rapid and efficient rejoining first, with the utilisation of additional steps or pathways of diminished accuracy if rejoining is unsuccessful or delayed. We evaluate the fidelity of DSB repair pathways and discuss how cancer cells promote the utilisation of less accurate processes. Homologous recombination serves to promote accuracy and stability during replication, providing a battlefield for cancer to gain instability. Non-homologous end-joining, a major DSB repair pathway in mammalian cells, usually operates with high fidelity and only switches to less faithful modes if timely repair fails. The transition step is finely tuned and provides another point of attack during tumour progression. In addition to DSB repair, a DSB signalling response activates processes such as cell cycle checkpoint arrest, which enhance the possibility of accurate DSB repair. We will consider the ways by which cancers modify and accost these processes to gain genomic instabilit

Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors

The Probabilistic Traveling Salesman Problem (PTSP) is a TSP problem in which each customer has a given probability of requiring a visit. The goal is to find an a priori tour of minimal expected length over all customers, with the strategy of visiting a random subset of customers in the same order as they appear in the a priori tour