rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
1997-10-21
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pubmed:abstractText |
The level and fate of hMSH3 (human MutS homolog 3) were examined in the promyelocytic leukemia cell line HL-60 and its methotrexate-resistant derivative HL-60R, which is drug resistant by virtue of an amplification event that spans the dihydrofolate reductase (DHFR) and MSH3 genes. Nuclear extracts from HL-60 and HL-60R cells were subjected to an identical, rapid purification protocol that efficiently captures heterodimeric hMutSalpha (hMSH2. hMSH6) and hMutSbeta (hMSH2.hMSH3). In HL-60 extracts the hMutSalpha to hMutSbeta ratio is roughly 6:1, whereas in methotrexate-resistant HL-60R cells the ratio is less than 1:100, due to overproduction of hMSH3 and heterodimer formation of this protein with virtually all the nuclear hMSH2. This shift is associated with marked reduction in the efficiency of base-base mismatch and hypermutability at the hypoxanthine phosphoribosyltransferase (HPRT) locus. Purified hMutSalpha and hMutSbeta display partial overlap in mismatch repair specificity: both participate in repair of a dinucleotide insertion-deletion heterology, but only hMutSalpha restores base-base mismatch repair to extracts of HL-60R cells or hMSH2-deficient LoVo colorectal tumor cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9294177-13518295,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10144-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9294177-DNA Repair,
pubmed-meshheading:9294177-DNA-Binding Proteins,
pubmed-meshheading:9294177-Drug Resistance, Microbial,
pubmed-meshheading:9294177-Fungal Proteins,
pubmed-meshheading:9294177-Gene Amplification,
pubmed-meshheading:9294177-HL-60 Cells,
pubmed-meshheading:9294177-Humans,
pubmed-meshheading:9294177-Methotrexate,
pubmed-meshheading:9294177-Mutation,
pubmed-meshheading:9294177-Nucleic Acid Heteroduplexes,
pubmed-meshheading:9294177-Tetrahydrofolate Dehydrogenase
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pubmed:year |
1997
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pubmed:articleTitle |
DHFR/MSH3 amplification in methotrexate-resistant cells alters the hMutSalpha/hMutSbeta ratio and reduces the efficiency of base-base mismatch repair.
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pubmed:affiliation |
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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