Human Molecular Genetics, Vol 7, 969-974, Copyright © 1998 by Oxford University Press
Y Matsumura, C Nishigori, T Yagi, S Imamura and H Takebe
Xeroderma pigmentosum (XP) complementation group F was first reported in
Japan and most XP-F patients reported to date are Japanese. The clinical
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 complex with ERCC1
and this complex functions as a structure- specific endonuclease
responsible for the 5' incision during DNA excision repair. Here we have
identified XPF mRNA mutations and examined levels of the mRNA 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) XPF proteins with amino acid
substitutions; (ii) amino acid substituted and truncated XPF proteins; and
(iii) truncated XPF protein only. A normal level of expression of XPF mRNA
was observed in XP-F cells but XPF protein was extremely low. These results
indicate that the detected mutations lead to unstable XPF protein,
resulting in a decrease in formation of the ERCC1-XPF endonuclease complex.
Slow excision repair of UV-induced DNA damage due to low residual
endonuclease activity provides a plausible explanation for the typical mild
phenotype of XP-F patients.
ARTICLES
Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-01, Japan.
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