CHINESE-HAMSTER CELLS MEET DNA-REPAIR - AN ENTIRELY ACCEPTABLE AFFAIR

This personal account relates the advent of mutant isolation and other developments in somatic cell genetics that were critical steps toward isolating DNA repair mutants in mammalian cells. The isolation of aux otrophic and temperature-sensitive mutants in genetically stable Chine se hamster cells during the late 1960s and early 1970s provided a conc eptual framework in which to later isolate mutations conferring hypers ensitivity to ultraviolet radiation, ionizing radiation, and various c hemical mutagens. Complementation group analysis of ultraviolet-sensit ive mutants helped identify multiple genes that overlapped with the gr oups of cancer-prone xeroderma pigmentosum, as well as Cockayne syndro me, The first mammalian cell mutants defective in strand-break repair were also discovered. Subsequent cloning of human genes that corrected CHO-cell mutations in nucleotide-excision repair groups 1-6 later led to identifying the key enzymes in the incision steps of this pathway, as well as the CSB protein, which is involved in coupling excision re pair and transcription. (C) 1998 John Wiley & Sons, Inc.dagger.