DNA LIGASE-I GENE-EXPRESSION DURING DIFFERENTIATION AND CELL-PROLIFERATION

We have studied the regulation of mammalian DNA ligase I gene by using a cDNA probe in Northern blot experiments with RNA extracted from several cell types in different growth conditions. DNA ligase I mRNA is detected in all analysed cell systems, regardless of their proliferation state, including mature rat neurons. A significant increase in DNA ligase I mRNA level is observed when cells are induced to proliferate, in agreement with the raise of DNA joining activity found in the same cell systems. The increase parallels the start of DNA synthesis, but the messenger remains at high level beyond the end of the S fase and is detected also in the presence of aphidicolin. A decrease in DNA ligase I mRNA is observed in HL-60 and NIH-3T3 cells after differentiation. The high stability of DNA ligase I mRNA in both resting and proliferating human fibroblasts suggests a cell proliferation dependent rate of transcription. On the other hand the presence of a basal level of DNA ligase I in nondividing cells, strongly suggests an involvement of this enzyme in DNA repair. This conclusion is supported by a threefold increase in DNA ligase I observed 24 h after UV irradiation of human confluent primary fibroblasts.