Source:http://linkedlifedata.com/resource/pubmed/id/17049932
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-1-2
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pubmed:abstractText |
Mutations of the Xpc gene cause a deficiency in global genome repair, a subpathway of nucleotide excision repair (NER), in mammalian cells. We used transgenic mice harboring the lambda-phage-based lacZ mutational reporter gene to study the effect of an Xpc null mutation (Xpc-/-) on damage induction, repair and mutagenesis in mouse skin epidermis after UVB irradiation. UVB induced equal amounts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (64PPs) in mouse skin epidermis of Xpc-/- and wild-type mice. CPDs were not significantly removed in either of the mouse genotypes by 12h after irradiation, whereas removal of 64PPs was observed in the wild-type. Irradiation with 300 and 400J/m2 UVB increased the lacZ mutant frequency in the Xpc-/- epidermis to at least twice as high as in the wild-type. Ninety-nine lacZ mutants isolated from the UVB-exposed epidermis of Xpc(-/-)mice were analyzed and compared with mutant sequences from irradiated wild-type mice. The spectra of the mutations in the two genotypes were both highly UV-specific and similar in the dominance of C-->T transitions at dipyrimidine sites; however, Xpc-/- mice had a higher frequency of two-base tandem substitutions, including CC-->TT mutations, three-base tandem substitutions and double base substitutions that were separated by one unchanged base in a three-base sequence (alternating mutations). These tandem/alternating mutations included a remarkably large number of triplet mutations, a recently reported, novel type of UV-specific mutation, characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. We concluded that the triplet mutation is a UV-specific mutation that preferably occurs in NER deficient genetic backgrounds.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1568-7864
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
82-93
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pubmed:meshHeading |
pubmed-meshheading:17049932-Animals,
pubmed-meshheading:17049932-DNA Repair,
pubmed-meshheading:17049932-DNA-Binding Proteins,
pubmed-meshheading:17049932-Epidermis,
pubmed-meshheading:17049932-Mice,
pubmed-meshheading:17049932-Mice, Knockout,
pubmed-meshheading:17049932-Mice, Transgenic,
pubmed-meshheading:17049932-Models, Animal,
pubmed-meshheading:17049932-Mutation,
pubmed-meshheading:17049932-Skin,
pubmed-meshheading:17049932-Ultraviolet Rays
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pubmed:year |
2007
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pubmed:articleTitle |
Frequent recovery of triplet mutations in UVB-exposed skin epidermis of Xpc-knockout mice.
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pubmed:affiliation |
Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan. ikehata@mail.tains.tohoku.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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