Linked Life Data

1933863

Source:http://linkedlifedata.com/resource/pubmed/id/1933863

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1991-11-25
pubmed:databankReference
pubmed:abstractText
Studies from several laboratories worldwide have developed a large database for in vivo hypoxanthine-guanine phosphoribosyltransferase gene mutations in human T-lymphocytes. Sufficient differences have been found thus far between the spectrum for spontaneous mutations in adults and that observed in the fetus to suggest fundamental differences in in vivo mutagenic mechanisms at these two life stages. In adults, only approximately 15% of hypoxanthine-guanine phosphoribosyltransferase mutations have structural alterations on Southern blots, while in the fetus 75% of mutations show alterations of which one-half are deletions of exons 2 and 3. We have now sequenced the breakpoint sites for these specific deletions in 18 mutant lymphocyte clones isolated from 13 normal newborns. Three classes of deletions were found. Each class had the same intron 1 breakpoint but a different intron 3 breakpoint. These mutations have all the signatures of a V(D)J recombinase-mediated event (a 5' consensus heptamer, 3' consensus heptamer and nonamer, nibbling, non-germline-encoded nucleotides, P-nucleotides). At the 3' breakpoint of the most common class (comprising 83% of the mutants) a perfect heptamer can be created by postulating a hairpin loop which could attain a Z-DNA configuration. This feature may indicate recombinase preference for certain DNA structures. These results implicate the V(D)J recombinase in illegitimate events causing mutation in this housekeeping gene during T-cell development. Inactivation of genes involved in the control of growth and differentiation (e.g., tumor suppressor genes) by this mechanism may have important implications for cancer development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6001-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1933863-Base Sequence, pubmed-meshheading:1933863-Cells, Cultured, pubmed-meshheading:1933863-Chromosome Deletion, pubmed-meshheading:1933863-Clone Cells, pubmed-meshheading:1933863-DNA Nucleotidyltransferases, pubmed-meshheading:1933863-Exons, pubmed-meshheading:1933863-Gene Expression Regulation, Enzymologic, pubmed-meshheading:1933863-Humans, pubmed-meshheading:1933863-Hypoxanthine Phosphoribosyltransferase, pubmed-meshheading:1933863-Infant, Newborn, pubmed-meshheading:1933863-Introns, pubmed-meshheading:1933863-Molecular Sequence Data, pubmed-meshheading:1933863-Mutation, pubmed-meshheading:1933863-Nucleic Acid Conformation, pubmed-meshheading:1933863-Oligodeoxyribonucleotides, pubmed-meshheading:1933863-Polymerase Chain Reaction, pubmed-meshheading:1933863-T-Lymphocytes, pubmed-meshheading:1933863-VDJ Recombinases
pubmed:year
1991
pubmed:articleTitle
V(D)J recombinase-like activity mediates hprt gene deletion in human fetal T-lymphocytes.
pubmed:affiliation
Environmental Health Research and Testing, Inc, Research Triangle Park, North Carolina 27709.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.