Functions that have been ascribed to several of the DNA repair genes include helicase, endonuclease, polymerase, ligase, and others not fully understood but somehow involved in recombination and repair processes. These known human genes have been found to be very similar to genes in yeast and even, in some cases, bacterial genes. Since we understand the DNA repair and metabolism systems much better in yeast and bacteria than in humans, we can begin with data from these model systems to understand human systems. The most severe of these diseases is xeroderma pigmentosum type D, which is characterized by high sensitivity to uv light, high cancer incidence, and some neurological disorders. Another of the diseases, Cockayne's syndrome, is characterized by slight photosensitivity and severe neurological defects but does not have a high cancer incidence.
Severity can vary.
Chris Webber at Livermore and collaborators have found mutations associated with these diseases throughout the entire gene but none can be associated absolutely with the phenotype. Protein folding and interaction in the complex may affect the form and phenotype produced. LLNL scientists Harvey Mohrenweiser and Richard Shen have measured variability in the coding sequences of some DNA repair genes in people. Some variants in the DNA sequence occur at high frequency and lead to nonconservative amino-acid changes in the protein. The next step is to link this information to populations that have increased susceptibility to disease.