DNA repair in human xeroderma pigmentosum group C cells involves a different distribution of damaged sites in...

Xeroderma pigmentosum is a human disease consisting of several complementation groups that are deficient in excision repair. Group C is one in which excision repair occurs at about 20-30% of normal levels. The distribution of mended sites in relation to unrepaired sites has been determined by cutting remaining unrepaired pyrimidine dimers with Microccocus luteus UV endonuclease. The mended sites have been found clustered together in a fashion that depended on cell proliferation. In confluent group C cells, the mended sites were clustered in regions where dimer excision was as efficient as excision in the DNA of normal cells. In proliferating group C cells, however, mended sites were randomly dispersed. The total amount of repair replication was the same in confluent and proliferating cells. Since previous work has shown that confluent group C cells show more extensive recovery from the lethal effects of UV irradiation than some other groups, clustered repair may correlate with a more efficient mechanism of restoring cell viability. The different distribution of repaired sites during DNA replication may be the result of changes in the state of the substrate for repair or changes in the metabolic priorities of DNA polymerases.