Human repair deficiencies and predisposition to cancer

The maintenance of genetic stability is essential to the viability of multicellular organisms. However, at the cellular level, the integrity of the genome is constantly challenged. Structural alterations continually appear in DNA, either spontaneously or as a result of environmental insult. Endogenously, base sequence modifications occur at a steady rate as byproducts of DNA metabolic transactions which habitually erode the accuracy of the encoded information. Organisms have, therefore, evolved a wide range of molecular mechanisms to cope with the requirement for cell survival by removing DNA damage and at the same time protecting the cell from the accumulation of deleterious mutations. These are the processes of DNA repair1. The proteins performing the functions of DNA repair are also encoded by the very DNA they protect and therefore mutations arising in genes coding for DNA repair proteins may inactivate or alter the repair processes themselves. The absence of DNA repair may prove fatal for individual cells in the face of DNA damage but, more importantly, is likely to be disastrous for a multicellular organism, where the unchecked accumulation of mutations may lead to accelerated tumorigenesis. From a human perspective, individuals with hereditary defects in DNA repair mechanisms may harbour an increased risk of cancer in their lifetime.