The Importance of Genome Maintenance

SUMMARY

The importance of genome maintenance is reflected in its role as a defense system against aging and cancer, as both are characterized by genomic instability. To study genome maintenance in the context of longevity, we investigated the genome of the naked mole rat (NMR). The NMR is the longest-lived rodent species, with a lifespan almost ten times longer than that of mice or rats. In addition to their longevity, naked mole rats also show an unusual resistance to cancer. By contrast, humans and mice are both prone to cancer, but the former is long lived whereas the latter is not. Here we address the question of whether these inter-species differences in life span and cancer resistance can be explained by differences in genome maintenance genes. Enabled by the recent sequencing of the naked mole rat genome, we cataloged the genome maintenance genes in the genomes of human, mouse, and naked mole rat and found major copy number variations among these three species.

DNA can be damaged by a myriad of exogenous and endogenous genotoxic agents, which makes the maintenance of DNA a fundamental and continuous challenge to every cell. Certain enzymes, such as superoxide dismutase, can lower the concentration of reactive oxygen species in the cell and thus reduce the overall DNA damage burden (Ikner and Shiozaki, 2005). DNA lesions nevertheless do occur and are then detected and repaired by multiple DNA repair systems (Friedberg, 2003). Genome maintenance is a complex process, requiring the coordination of multiple cellular activities, including DNA repair (Lagerwerf et al., 2011), cell cycle control (Diallo and Prigent, 2011), and checkpoint monitoring (Machida and Dutta, 2005). This process occasionally fails, leading to genomic in...

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