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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
1998-10-22
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pubmed:databankReference | |
pubmed:abstractText |
Nucleotide excision repair (NER) is an important cellular defense mechanism which protects the integrity of the genome by removing DNA damage caused by UV-light or chemical agents. In humans, defects in the NER pathway result in the disease xeroderma pigmentosum (XP) which is characterized by increased UV-sensitivity, with increased propensity for skin cancer, and an array of developmental abnormalities. Some XP patients exhibit, in addition, symptoms of Cockayne's syndrome (CS) and trichothiodystrophy (TTD), which are characterized by increased UV-sensitivity, without increased cancer incidence, and an array of developmental abnormalities. Some NER genes, including the DNA helicases XPB and XPD, have been shown to function in transcription as well as repair, by virtue of being an integral part of the transcription initiation factor TFIIH. This dual function may account for the above-mentioned wide pleiotropy of phenotypes associated with defects in NER genes, and may explain why some XP patients exhibit developmental abnormalities in addition to XP symptoms. To date, only five XPB patients with three different mutations in the XPB gene have been reported. One of these mutations is a C to A transversion at the splice site at the beginning of the last exon, which resulted in a frameshift throughout the last exon. This patient shows combined clinical symptoms of XP and CS. The recent cloning of the repB gene, the Dictyostelium discoideum homolog of XPB, allowed us to generate a similar C-terminal mutation in the Dictyostelium, in order to test whether the defect in this NER gene has an effect on growth or development. To this end, we have constructed a C-terminal deletion repB mutant in Dictyostelium. To avoid the possibility that a null mutant would be lethal, we used direct homologous recombination to create a 46 amino acid C-terminal deletion mutant. Indeed, we were unable to obtain mutants with a longer 95 amino acid deletion. The repB delta C46 mutants showed an increased sensitivity to UV-light, but a normal pattern of UV-induced expression of repair genes, and no immediately obvious defect in either growth rate or development. The results suggest that the associated developmental defects in the human XPB patients may be due to mutations in another gene.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RepB protein, Bacteria,
http://linkedlifedata.com/resource/pubmed/chemical/XPBC-ERCC-3 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
20
|
pubmed:volume |
1399
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
161-72
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9765592-Amino Acid Sequence,
pubmed-meshheading:9765592-Animals,
pubmed-meshheading:9765592-Bacterial Proteins,
pubmed-meshheading:9765592-Blotting, Northern,
pubmed-meshheading:9765592-Blotting, Southern,
pubmed-meshheading:9765592-DNA Helicases,
pubmed-meshheading:9765592-DNA Repair,
pubmed-meshheading:9765592-DNA-Binding Proteins,
pubmed-meshheading:9765592-Dictyostelium,
pubmed-meshheading:9765592-Gene Deletion,
pubmed-meshheading:9765592-Molecular Sequence Data,
pubmed-meshheading:9765592-Mutation,
pubmed-meshheading:9765592-Plasmids,
pubmed-meshheading:9765592-RNA, Messenger,
pubmed-meshheading:9765592-Restriction Mapping,
pubmed-meshheading:9765592-Sequence Alignment,
pubmed-meshheading:9765592-Ultraviolet Rays,
pubmed-meshheading:9765592-Xeroderma Pigmentosum
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pubmed:year |
1998
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pubmed:articleTitle |
A mutation in repB, the dictyostelium homolog of the human xeroderma pigmentosum B gene, has increased sensitivity to UV-light but normal morphogenesis.
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pubmed:affiliation |
Division of Biological Sciences, University of Missouri, Columbia 65211-7400, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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