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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
1997-9-8
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pubmed:abstractText |
The spectrum of mutations induced by the naturally occurring DNA adduct pyrimido[1,2-alpha]purin-10(3H)-one (M1G) was determined by site-specific approaches using M13 vectors replicated in Escherichia coli. M1G was placed at position 6256 in the (-)-strand of M13MB102 by ligating the oligodeoxynucleotide 5'-GGT(M1G)TCCG-3' into a gapped-duplex derivative of the vector. Unmodified and M1G-modified genomes containing either a cytosine or thymine at position 6256 of the (+)-strand were transformed into repair-proficient and repair-deficient E. coli strains, and base pair substitutions were quantitated by hybridization analysis. Modified genomes containing a cytosine opposite M1G resulted in roughly equal numbers of M1G-->A and M1G-->T mutations with few M1G-->C mutations. The total mutation frequency was approximately 1%, which represents a 500-fold increase in mutations compared with unmodified M13MB102. Transformation of modified genomes containing a thymine opposite M1G allowed an estimate to be made of the ability of M1G to block replication. The (-)-strand was replicated >80% of the time in the unadducted genome but only 20% of the time when M1G was present. Correction of the mutation frequency for the strand bias of replication indicated that the actual frequency of mutations induced by M1G was 18%. Experiments using E. coli with different genetic backgrounds indicated that the SOS response enhances the mutagenicity of M1G and that M1G is a substrate for repair by the nucleotide excision repair complex. These studies indicate that M1G, which is present endogenously in DNA of healthy human beings, is a strong block to replication and an efficient premutagenic lesion.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1423861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1429591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1438275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1883202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1888735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-1944345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-2079232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-491777,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-6339098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7634413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-766187,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7697821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7780968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7834810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7961843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-7991554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8079172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8117915,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8205535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8251500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8318654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8469282,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8471617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8597138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8621568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8640909,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8653695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8784204,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-8924603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-9049429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-9111054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9238032-9168253
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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 |
Aug
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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 |
5
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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 |
8652-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9238032-DNA, Bacterial,
pubmed-meshheading:9238032-DNA Adducts,
pubmed-meshheading:9238032-Escherichia coli,
pubmed-meshheading:9238032-Humans,
pubmed-meshheading:9238032-Malondialdehyde,
pubmed-meshheading:9238032-Mutagenesis, Site-Directed,
pubmed-meshheading:9238032-Mutation,
pubmed-meshheading:9238032-Purines,
pubmed-meshheading:9238032-Pyrimidines
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pubmed:year |
1997
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pubmed:articleTitle |
Mutagenicity in Escherichia coli of the major DNA adduct derived from the endogenous mutagen malondialdehyde.
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pubmed:affiliation |
Department of Biochemistry, Center in Molecular Toxicology and The Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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