Y. Matsumura et al., CHARACTERIZATION OF MOLECULAR DEFECTS IN XERODERMA-PIGMENTOSUM GROUP-F IN RELATION TO ITS CLINICALLY MILD SYMPTOMS, Human molecular genetics, 7(6), 1998, pp. 969-974
Xeroderma pigmentosum (XP) complementation group F was first reported
in Japan and most XP-F patients reported to date are Japanese. The cli
nical features of XP-F patients are rather mild, including late onset
of skin cancer. Recently a cDNA that corrects the repair deficiency of
cultured XP-F cells was isolated, The XPF protein forms a tight compl
ex with ERCC1 and this complex functions as a structure-specific endon
uclease responsible for the 5' incision during DNA excision repair. He
re we have identified XPF mRNA mutations and examined levels of the mR
NA and protein expression in seven primary cell strains from Japanese
XP-F patients. The XP-F cell strains were classified into three types
in terms of the effect of the mutation on the predicted protein; (i) X
PF proteins with amino acid substitutions; (ii) amino acid substituted
and truncated XPF proteins; and (iii) truncated XPF protein only. A n
ormal level of expression of XPFmRNA was observed in XP-F cells but XP
F protein was extremely low. These results indicate that the detected
mutations lead to unstable XPF protein, resulting in a decrease in for
mation of the ERCC1-XPF endonuclease complex. Slow excision repair of
UV-induced DNA damage due to low residual endonuclease activity provid
es a plausible explanation for the typical mild phenotype of XP-F pati
ents.