Choices have consequences: the nexus between DNA repair pathways and genomic instability in cancer.

Background: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored. Main body: The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is considered to be error-prone, intrinsically mutagenic quick fix remedy to seal together the broken DNA ends and restart replication. In contrast, HR is a high-fidelity process that has been very well conserved from phage to humans. Here we review HR and its sub-pathways. We discuss what factors determine the sub pathway choice including etiology of the DSB, chromatin structure at the break site, processing of the DSBs and the mechanisms regulating the sub-pathway choice. We also elaborate on the potential of targeting HR genes for cancer therapy and anticancer strategies. Conclusion: The DNA repair field is a vibrant one, and the stage is ripe for scrutinizing the potential treatment efficacy and future clinical applications of the pharmacological inhibitors of HR enzymes as mono- or combinatorial therapy regimes. [ABSTRACT FROM AUTHOR]

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