Postreplication repair: questions of its definition and possible alteration in xeroderma pigmentosum cell strains

Abstract

DNA synthesis in normal cells and in excision-defective and variant xeroderma pigmentosum cells was investigated after irradiation with ultraviolet light. The sizes of DNA synthesized during brief pulses of [3H]thymidine 1-2 hr after irradiation were decreased, the xeroderma pigmentosum variant showing the smallest molecular weight. Once synthesized, however, labeled DNA increased in size at the same rat as control in all cell strains, and the rate was relatively insensitive to caffeine. After 2-3 hr, labeled DNA in each cell type reached a maximum size that was less than that in control cells, indicating the presence of long-lived blocks to DNA chain growth. This kind of experiment (pulse-chase) has in the past been used to investigate a repair process believed to be associated with the bypass of damaged sites in parental DNA: postreplication repair. We present an alternative model that does not involve a specific postreplication repair mechanism, but involve a specific postreplication repair mechanism, but involves normal chain elongation and termination mechanisms in which we conceive that dimers and other damaged sites act as well-or-nothing blocks to the progress of replication forks. No evidence could be found for any inducible process that enhanced the bypass of damaged sites.