DIFFERENTIAL CELL-CYCLE MODULATION OF HUMAN DNA GLYCOSYLASES AGAINST OXIDIZED PYRIMIDINES

Cellular DNA is continuously subject to damages by both endogenous and exogenous oxidizing agents. Excision repair of oxidized bases in human cells is initiated by DNA glycosylases which remove them from DNA. 5-Hydroxymethyluracil-DNA glycosylase excises 5-hydroxymethyluracil from DNA. A different enzyme, termed a redoxyendnuclease, has glycosylase activity against many modified DNA pyrimidines. The regulation of these enzymes in proliferating human cells was examined. Both glycosylases were assayed in serum-stimulated WI-38 cells by measurements of direct release of modified free bases from their respective DNA substrates. There was no significant variation of 5-hydroxymethyluracil-DNA glycosylase activity during the cell cycle. However, the glycosylic activity of the redoxyendonuclease was stimulated with DNA synthesis. Thi activity again increased at the beginning of a second cell cycle. Therefore, the glycosylases that initiate excision repair of oxidized DNA are subject to different controls during the cell cycle. © 1990.