Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90157
Title:
Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations.
Authors:
Boyle, John M; Greaves, Martin J; Camplejohn, R S; Birch, Jillian M; Roberts, Stephen A; Varley, Jennifer
Abstract:
Radiation-induced G1 arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon-intron boundaries, 3' and 5' untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G1 arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/-) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent.
Affiliation:
CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, UK.
Citation:
Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations. 1999, 79 (11-12):1657-64 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Apr-1999
URI:
http://hdl.handle.net/10541/90157
DOI:
10.1038/sj.bjc.6690265
PubMed ID:
10206274
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBoyle, John Men
dc.contributor.authorGreaves, Martin Jen
dc.contributor.authorCamplejohn, R Sen
dc.contributor.authorBirch, Jillian Men
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorVarley, Jenniferen
dc.date.accessioned2010-01-20T15:53:23Z-
dc.date.available2010-01-20T15:53:23Z-
dc.date.issued1999-04-
dc.identifier.citationRadiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations. 1999, 79 (11-12):1657-64 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid10206274-
dc.identifier.doi10.1038/sj.bjc.6690265-
dc.identifier.urihttp://hdl.handle.net/10541/90157-
dc.description.abstractRadiation-induced G1 arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon-intron boundaries, 3' and 5' untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G1 arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/-) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent.en
dc.language.isoenen
dc.subject.meshAlleles-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshFibroblasts-
dc.subject.meshG1 Phase-
dc.subject.meshHeterozygote Detection-
dc.subject.meshHumans-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshMutation-
dc.subject.meshSaccharomyces cerevisiae-
dc.titleRadiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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