DNA integrity is always under attack from environmental agents like skin cancer-causing UV rays. How do DNA repair mechanisms detect and repair damaged DNA, and what happens when they fail? Aa  Aa  Aa Table 1 Because  DNA  is the repository of genetic information in each living  cell, its integrity and  stability  are essential to life. DNA, however, is not inert; rather, it is a chemical entity subject to assault from the  environment, and any resulting damage, if not repaired, will lead to  mutation  and possibly  disease. Perhaps the best-known example of the link between environmental-induced DNA damage and disease is that of skin  cancer, which can be caused by excessive exposure to UV  radiation  in the form of sunlight (and, to a lesser degree, tanning beds). Another example is the damage caused by tobacco smoke, which can lead to mutations in lung cells and subsequent cancer of the lung. Beyond environmental agents, DNA is also subject to oxidative damage from byproducts of  metabolism, such as free radicals. In fact, it has been estimated that an individual cell can suffer up to one million DNA changes per day (Lodish  et al., 2005). In addition to genetic insults caused by the environment, the very process of DNA  replication  during  cell division  is prone to error. The rate at which  DNA polymerase  adds incorrect nucleotides during DNA replication is a major factor in determining the spontaneous  mutation rate  in an  organism. While a "proofreading"  enzyme  normally recognizes and corrects many of these errors, some mutations survive this process. Estimates of the  frequency  at which human DNA undergoes lasting, uncorrected errors range from 1 x 10-4  to 1 x 10-6mutations per  gamete  for a given  gene. A rate of 1 x 10-6  means that a scientist would expect to find one mutation at a specific  locus  per one milliongametes. Mutation rates in other organisms are often much lower (Table 1). One way scientists are able to estimate mutation rates is by considering the rate of new  dominant  mutations found at different loci. For example, by examining the number of individuals in a given  population  who were diagnosed with  neurofibromatosis  (NF1, a disease caused by a spontaneous ”or noninherited ”dominant mutation), scientists determined that the  spontaneous mutation  rate of the gene responsible for this disease averaged 1 x 10-4mutations per gamete (Crowe  et al., 1956). Other researchers have found that the mutation rates of other  genes, like that for Huntington's disease, are significantly lower than the rate for NF1. The fact that investigators have reported different mutation rates for different genes suggests that certain loci are more prone to damage or error than others. DNA Repair Mechanisms and Human Disease Table 2 Figure Detail Figure 1 DNA repair  processe