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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1996-2-22
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pubmed:abstractText |
High-density mutational spectra have been established for exon 3 of the gene encoding adenine phosphoribosyltransferase (APRT) of the Chinese hamster ovary (CHO) cell line derivative D422 and closely related and/or modified lines by using the mutagen ethyl methanesulfonate (EMS). The total number of selectable sites (GC-->AT transitions yielding a selectable APRT- phenotype) was estimated at 31 based on our own accumulated data base of 136 sequenced exon 3 mutations and on literature reports. D422 and two other APRT hemizygous lines each yielded very similar spectra and showed two populations of mutable sites: (i) 24 "baseline" sites that followed the Poisson distribution and therefore were equally susceptible to mutation and (ii) two hotspots, one comprising a cluster at nucleotides 1293-1309 and the other at nucleotide 1365. Collectively, the latter sites were about 10-fold more frequently mutated than the others. CHO cells are mer- as they lack the repair enzyme O6-methylguanidine methyltransferase (EC 2.1.1.63). In modified repair-proficient CHO cells, the distribution of mutations among all of the 31 sites was random, with only 3 of the 19 GC-->AT transitions in the above hotspots. To determine whether the distribution was locus-dependent, two independent lines carrying single copies of transfected APRT genes were generated from a derivative of D422 carrying a deletion in the endogenous APRT gene. Nucleotides 1293-1309 were again no longer preferentially mutated, but the site at nucleotide 1365 was still a hotspot. We conclude that mutational spectra in mer- cells are at least in part locus dependent and that some sequences are particularly susceptible to EMS mutagenesis and perhaps also to methyltransferase repair.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1373832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1383728,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1423294,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1511435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1540967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1655249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1657427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1675490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1710024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1717694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1899056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-1993655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-2233815,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-2488705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-2536133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-2649264,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-2687159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3041622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3044636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3052269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3205718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3305959,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-3525535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-4370211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-5791738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-6256643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-6271971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-6589795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-6854650,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-7101104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-7686256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-7806327,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-7991608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-8033107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-8231820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-8420940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8552587-8439973
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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 |
Jan
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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 |
9
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
121-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8552587-Adenine Phosphoribosyltransferase,
pubmed-meshheading:8552587-Animals,
pubmed-meshheading:8552587-Base Composition,
pubmed-meshheading:8552587-Base Sequence,
pubmed-meshheading:8552587-CHO Cells,
pubmed-meshheading:8552587-Cricetinae,
pubmed-meshheading:8552587-DNA Repair,
pubmed-meshheading:8552587-Ethyl Methanesulfonate,
pubmed-meshheading:8552587-Exons,
pubmed-meshheading:8552587-Methyltransferases,
pubmed-meshheading:8552587-Molecular Sequence Data,
pubmed-meshheading:8552587-Mutagens,
pubmed-meshheading:8552587-O(6)-Methylguanine-DNA Methyltransferase,
pubmed-meshheading:8552587-Point Mutation,
pubmed-meshheading:8552587-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:8552587-Structure-Activity Relationship
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pubmed:year |
1996
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pubmed:articleTitle |
Influence of alkyltransferase activity and chromosomal locus on mutational hotspots in Chinese hamster ovary cells.
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pubmed:affiliation |
Institut du cancer de Montréal, Centre de Recherche Louis-Charles Simard, Montréal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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