Linked Life Data

12112308

Source:http://linkedlifedata.com/resource/pubmed/id/12112308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-7-11
pubmed:abstractText
We have systematically varied microsatellite sequence composition to determine the effects of repeat unit size, G+C content, and DNA secondary structure on microsatellite stability in human cells. The microsatellites were inserted in frame within the 5' region of the herpes simplex virus thymidine kinase (HSV-tk) gene. The polypyrimidine/polypurine microsatellites displayed enhanced S1 nuclease sensitivity in vitro, consistent with the formation of non-B-form DNA structures. Microsatellite mutagenesis studies were performed with a shuttle vector system in which inactivating HSV-tk mutations are measured after replication in a nontumorigenic cell line. A significant increase in the HSV-tk mutation frequency per cell generation was observed after insertion of [TTCC/AAGG]9, [TTTC/AAAG]9, or [TCTA/AGAT]9 sequences (P <or= 0.0002), relative to the HSV-tk gene control. We observed that the G + C content of the microsatellite may affect mutagenesis, as the mean microsatellite mutation rates of the [TTTC/AAAG]9 and [TCTA/AGAT]9 alleles were sevenfold and 11-fold higher, respectively, than the [TTCC/AAGG]9 allele. A bias toward expansion mutations was noted for the majority of clones bearing the [TTCC/AAGG]9 allele as well as a [TC/AG]17 microsatellite of similar allele length. The mean microsatellite mutation rate of the [TTCC/AAGG]9 allele did not differ significantly from that for a [TC/AG]11 allele, demonstrating that these tetranucleotide and dinucleotide alleles are of equivalent stability. It is known that microsatellite mutagenesis is affected by the number of repeat units within an allele. Our data suggest that additional biochemical factors may regulate both the rate and specificity of somatic cell microsatellite mutagenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0899-1987
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
140-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Mutation rate and specificity analysis of tetranucleotide microsatellite DNA alleles in somatic human cells.
pubmed:affiliation
Jake Gittlen Cancer Research Institute, Department of Pathology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.