Abstract
Rational thinking builds on feelings, too. This article starts with a tribute to Richard Setlow, an eminent scientist; it retraces as well some studies in molecular genetics that helped to understand basic questions of radiation biology. In the midโ1950s, the induction of a dormant virus (prophage) by irradiation of its host was an intriguing phenomenon. Soon, it was found that prophage induction results from the inactivation of the prophage repressor. Similarly, a score of induced cellular SOS functions were found to be induced when the LexA repressor is inactivated. Repressor inactivation involves the formation of a newly formed distinctive structure: a RecAโpolymer wrapped around singleโstranded DNA left by the arrest of replication at damaged sites. By touching this RecA nucleofilament, the LexA repressor is inactivated, triggering the sequential expression of SOS functions. The RecA nucleofilament acts as a chaperone, allowing recombinational repair to occur after nucleotide excision repair is over. The UmuDโฒC complex, synthesized slowly and parsimoniously, peaks at the end of recombinational repair, ready to be positioned at the tip of a RecA nucleofilament, placing the UmuDโฒC complex right at a lesion. At this location, UmuDโฒC prevents recombinational repair, and now acts as an errorโprone paucimerase that fills the discontinuity opposite the damaged DNA. Finally, the elimination of lesions from the path of DNA polymerase, allows the resumption of DNA replication, and the SOS repair cycle switches to a normal cell cycle. Environ. Mol. Mutagen. 38:135โ143, 2001. ยฉ 2001 WileyโLiss, Inc.