"Close-fitting sleeves"--recognition of structural defects in duplex DNA.
The first step in the ubiquitous cellular process of nucleotide excision-repair must involve the recognition of a lesion or structural distortion in DNA. This is followed by incision in the strand perceived as damaged; and then coordinated steps of local degradation and re-synthesis occur to replace the defective DNA segment with a new stretch of nucleotides, making use of the intact complementary strand as template. The repair patch is ultimately ligated at its 3' end to the contiguous preexisting DNA strand to restore the integrity of the normal DNA structure. Crucial to this repair scheme is the fact that the genome consists of double-stranded DNA, so that when one strand is damaged the information for its repair can, in principle, be recovered from the other strand. We will review a bit of the early speculation about the nature of the damage recognition step and then discuss the complexity of that event as we currently understand it. An important conceptual contribution to this field resulted from my collaboration with Robert Haynes in which we suggested that "the recognition step in the repair mechanism could be formally equivalent to threading the DNA through a close-fitting 'sleeve' which gauges the closeness-of-fit to the Watson-Crick structure" (Hanawalt and Haynes, 1965).
Hanawalt
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Department of Biological Sciences, Herrin Laboratories, Stanford University, CA 94305-5020.
D004249:DNA Damage; D004260:DNA Repair; D008957:Models, Genetic; D014158:Transcription, Genetic