Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.
UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic DNA and from the nontranscribed strand of an expressed gene. Expression of p48 suppressed UV-induced mutations arising from the nontranscribed strand, but had no effect on cellular UV sensitivity. These results define the role of p48 in DNA repair, demonstrate the importance of CPDs in mutagenesis, and suggest how rodent models can be improved to better reflect cancer susceptibility in humans.
Tang
J Y
JY
Department of Medicine, Stanford University, California 94305, USA.
Hwang
B J
BJ
Ford
J M
JM
Hanawalt
P C
PC
Chu
G
G
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D051379:Mice; D016296:Mutagenesis; D011740:Pyrimidine Dimers; D012377:Rodentia / Q000235:genetics*; D013045:Species Specificity; D014158:Transcription, Genetic; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000235:genetics*
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D007041:Hypoxanthine Phosphoribosyltransferase