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Heterokaryons between fibroblasts from patients with classical Xeroderma pigmentosum (X.P.) and fibroblasts from normal or heterozygous subjects have indicated that normal cells contain at least three- to fourfold the amount of ‘X.P.-enzyme’ necessary for maximal unscheduled DNA synthesis and that the reduced enzyme levels in heterozygotes can be detected using heterokaryons with a high ratio of X.P. to heterozygous nuclei. Furthermore, a kinetic study of complementation in heterokaryons suggests that the ‘X.P.-enzyme’ is, probably, not a monomer and that its function may be dependent upon binding to an acceptor and formation of a stable complex which turns over slowly. Patients with the same clinical form of X.P. (classical type) may carry defective enzymes which do or do not bind to the acceptor. Our findings and the evidence in favour of a close correlation in the kinetics of the different aspects of the excision repair of DNA prompt us to suggest that the enzymes of this repair system may assemble to form a ‘repair organelle’.

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Patients with Xeroderma pigmentosum and defective DNA excision repair can be distinguished as a rapid (r-XP) and slow (s-XP) complementing variety. When fused with normal cells, fibroblasts from the r-XP are complemented rapidly and in the absence of protein synthesis while those from the s-XP are complemented slowly by a process partly, but not entirely, dependent on protein synthesis. Heterokaryons with different ratios of r-XP to s-XP nuclei (i.e. 1:1-5 and 1-5:1) and control heterokaryons containing one normal and 1-5 r- or s-XP nuclei show that if cell fusion and incubation is conducted in medium preventing protein synthesis, the rXP cells do not complement the s-XP partner at all and, conversely, that the latter is not as effective as normal cells at complementing the rXP partner. On the contrary, if protein synthesis is permitted, the 2 types of XP cells complement each other in a gene dose-dependent manner and to an extent similar to that observed in the control heterokaryons. These findings indicate that the r- and s-XP varieties are caused by mutations at different loci and suggest that the products of these loci interact to produce a functional unit which is present in normal control cells but absent in the XP strains. The relationship between the complementation groups described here and those already reported in the literature being investigated.