A re-examination of the intragenome distribution of repaired sites in proliferating xeroderma pigmentosum complementation group C fibroblasts.

We find that rapidly proliferating fibroblasts from xeroderma pigmentosum complementation group C (XP-C) patients, cells that have a small residual DNA excision repair capacity, repair DNA in localized regions of the genome in a clustered pattern rather than at single sites in dispersed locations. This finding is similar to that observed earlier for nondividing cells but is in contrast to published results that indicate that the residual repair in proliferating XP-C cells is dispersed throughout the genome in a non-clustered pattern. While we detect the same amount of repair in both proliferating and nondividing cells, we also observe no shift from the clustered pattern of repair to a more dispersive pattern when nondividing cells are stimulated to proliferate by fresh serum addition. We have no obvious explanation for these discrepancies with the published results. We have noted previously that proliferating XP-C cells are very UV sensitive relative to normal cells while nondividing cells that exhibit the same amount of repair activity are relatively UV resistant. There is no satisfactory explanation for this change in relative response to the lethal effects of UV, a change not observed for cell strains from other XP complementation groups. However, we argue that clustered repair in specific genomic regions promotes survival in nondividing XP-C cells but does not promote survival in proliferating cells.