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Nucleases Involved in DNA Repair

Stuart Linn


DNA repair has traditionally been a subject of extensive review and documentation. Therefore, this article will concentrate upon deoxyribonucleases that are directly implicated in the phenomena. Recent reviews and monographs concerning other aspects of DNA repair include Hanawalt et al. (1978 Hanawalt et al. (1979), Bernstein (1981), Friedberg et al. (1981), Seeberg and Kleppe (1981), and Sutherland (1981).

Directly associating a nuclease or other protein with a role in DNA repair is a difficult task for several reasons. The difficulties are particularly true in animal cells where, for example, to date no enzyme defect has been correlated with the symptoms of any “repair-deficiency disease.” In human cells, where repair-deficiency diseases are the major source of “mutants,” it ought to be noted that persons with these diseases still carry out the large majority of DNA repair that is necessary for survival and development, so that in fact one might expect biochemical deficiencies in these cells to be relatively subtle. Indeed, as noted below, there are alternative pathways and enzymes for dealing with specific lesions, so that mutants lacking specific enzymes might be expected to have weak or no phenotypic response.

Another problem is that the number of loci associated with each phenotype is often inexplicably large. For example, there are more than 50 DNA repair loci in yeast and probably an equal number of such loci in Escherichia coli. In human cells there are at least seven complementation groups of xeroderma pigmentosum (XP) and three of ataxia telangiectasia. Trying to identify an enzyme...

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