DNA repair and genetic diseases in humans
Several genetic diseases in human beings are characterized by cellular hypersensitivity to DNA damage. These diseases also cause increased risk of cancer. Four such recessively inherited diseases include the following : (i) Fanconi anaemia (FA); (ii) Xeroderma pigmentosum (XP);
(iii) Ataxia telangiectasia (AT)
and (iv) Bloom's syndrome
(BS); cells from patients with the first three diseases are uniquely sensitive to DNA damage by DNA cross-linking agents, ultraviolet light and ionizing radiations respectively, those with BS are moderately hypersensitive to several agents causing different types of DNA damage. Genes responsible for two of these diseases (FA, XP) have been identified recently by complementation of hypersensitive cell lines using DNA expression cloning technology (see Genetic Engineering and Biotechnology 1. Recombinant DNA and PCR (Cloning and Amplification of DNA)
for cloning). The XP DNA products show significant similarity to the products of the RAD DNA repair gene of budding yeast, and ERCC genes of rodents (Table 26.7), which are involved in the nucleotide excision repair showing that the essential enzymes involved in DNA metabolism have been conserved through evolution. In future more work on the molecular mechanism of these diseases involving DNA damage will be done.