CHARACTERIZATION OF MOLECULAR DEFECTS IN XERODERMA-PIGMENTOSUM GROUP-F IN RELATION TO ITS CLINICALLY MILD SYMPTOMS

Citation
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
Citations number
21
Categorie Soggetti
Genetics & Heredity",Biology
Journal title
ISSN journal
09646906
Volume
7
Issue
6
Year of publication
1998
Pages
969 - 974
Database
ISI
SICI code
0964-6906(1998)7:6<969:COMDIX>2.0.ZU;2-Y
Abstract
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.