Induction and repair of (6-4) photoproducts in normal human and xeroderma pigmentosum variant cells during the cell cycle.

Abstract

The reduced rate of (6-4) photoproduct repair observed in some cell lines may represent a more severe repair deficiency in some cohort of the cell cycle, such as S-phase. Radioimmunoassay was used to determine the kinetics of (6-4) photoproduct repair in normal human fibroblasts and xeroderma pigmentosum variant cells fractionated into different phases of the cell cycle by counterflow centrifugal elutriation. Ultraviolet fluence response curves indicated that the same amount of (6-4) photoproduct damage was induced at all phases of the cell cycle. The extent of (6-4) photoproduct repair in asynchronous XP variant cells was significantly reduced compared to normal human cells. However, the rate and extent of (6-4) photoproduct repair was constant throughout the cell cycle in both normal and XP variant cells. Hence, the UV hypersensitive and hypermutable phenotypes observed in XP variant cells are not attributable to cell cycle-dependent deficiencies in excision repair nor the yield of photodamage through the cell cycle.