GENE-SPECIFIC REPAIR IN HUMAN CD4(+) LYMPHOCYTES REFLECTS TRANSCRIPTION AND PROLIFERATION

We have measured the gene-specific repair of ultraviolet irradiation ( UV)-induced cyclobutane pyrimidine dimers (CPD) in freshly isolated hu man peripheral blood CD4(+) T-lymphocytes. Two populations of CD4(+) l ymphocytes were assayed: resting and proliferating cells. DNA repair w as assessed in the essential gene dihydrofolate reductase (DHFR) as we ll as in each of its strands, in the proliferation inducible c-myc gen e and in the inactive delta-globin gene. Transcription rates in these genes were determined by nuclear run-on assay in the two cell populati ons. The rate of DHFR transcription increased 10-fold from resting to proliferating lymphocytes. Transcripts from c-myc were present only in proliferating cells, and we detected no delta-globin transcripts in e ither cell population. During the 24-h period after UV irradiation, th ere was little or no repair in any of the genes in the resting cells; there was some repair in the transcribed strand of the DHFR gene, but no repair in its nontranscribed strand. In the proliferating cells whe re the transcription of DHFR was much increased, the repair was effici ent. The delta-globin gene was not expressed in either cell population , but it was more efficiently repaired in the proliferating than in th e resting cells. We suggest that the gene-specific repair activity in CD4(+) lymphocytes can reflect the proliferative state of the cells as well as the transcriptional state of the gene.