Abstract
The lesion-specific DNA polymerase POLH gene is mutated in xeroderma pigmentosum variant (XP-V) patients who exhibit an increased skin cancer incidence from UV exposure. Normal cells in which POLH expression was reduced using short interfering RNAs (siRNAs) were compared with the XP-V cellular phenotype that results from naturally occurring inactivating mutations. Stable clones expressing siRNA had partially reduced POLH protein levels, and intermediate levels of UV sensitivity and S phase checkpoint activation, but similar levels of Mre11 foci as in XP-V cells. Therefore, suppression of POLH expression levels by siRNA recapitulates most of the phenotypes seen in cells from XP-V patients with inactivating mutations in POLH.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Caffeine / pharmacology
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Cell Line, Transformed
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DNA-Directed DNA Polymerase / genetics
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Endodeoxyribonucleases / genetics
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Exodeoxyribonucleases / genetics
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Fibroblasts / enzymology
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Fibroblasts / physiology
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Fibroblasts / radiation effects
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Humans
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Nucleic Acid Synthesis Inhibitors*
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Plasmids / genetics
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RNA, Small Interfering / genetics*
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S Phase / genetics
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S Phase / radiation effects
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Saccharomyces cerevisiae Proteins / genetics
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Transfection
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Ultraviolet Rays / adverse effects
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Xeroderma Pigmentosum / enzymology*
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Xeroderma Pigmentosum / genetics*
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Xeroderma Pigmentosum / prevention & control
Substances
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Nucleic Acid Synthesis Inhibitors
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RNA, Small Interfering
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Saccharomyces cerevisiae Proteins
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Caffeine
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DNA-Directed DNA Polymerase
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Rad30 protein
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Endodeoxyribonucleases
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Exodeoxyribonucleases
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MRE11 protein, S cerevisiae