Dna repair synthesis in human heterokaryons: II. a test for heterozygosity in xeroderma pigmentosum and some insight into the structure of the defective enzyme

Abstract

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’.