Linked Life Data

19040636

Source:http://linkedlifedata.com/resource/pubmed/id/19040636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-23
pubmed:abstractText
As a first step towards describing the role of proteolysis in maintaining genomic integrity, we have determined the effect of the loss of ClpXP, a major energy-dependent cytoplasmic protease that degrades truncated proteins as well as a number of regulatory proteins, on spontaneous mutagenesis. In a rifampicin-sensitive to rifampicin-resistance assay that detects base substitution mutations in the essential rpoB gene, there is a modest, but appreciable increase in mutagenesis in Delta(clpP-clpX) cells relative to wild-type cells. A colony papillation analysis using a set of lacZ strains revealed that genetic -1 frameshift mutations are strongly elevated in Clp-defective cells. A quantitative analysis using a valine-sensitive to valine-resistance assay that detects frameshift mutations showed that mutagenesis is elevated 50-fold in Clp-defective cells. Elevated frameshift mutagenesis observed in Clp-deficient cells is essentially abolished in lexA1[Ind(-)] (SOS-uninducible) cells, and in cells deleted for the SOS gene dinB, which codes for DNA polymerase IV. In contrast, mutagenesis is unaffected or stimulated in cells deleted for umuC or umuD, which code for critical components of DNA polymerase V. Loss of rpoS, which codes for a stress-response sigma factor known to upregulate dinB expression in stationary phase, does not affect mutagenesis. We propose that elevated DinB expression, as well as stabilization of UmuD/UmuD' heterodimers in Delta(clpP-clpX) cells, contributes to elevated mutagenesis. These findings suggest that in normal cells, Clp-mediated proteolysis plays an important role in preventing gratuitous mutagenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1365-2958
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
629-39
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Spontaneous mutagenesis is elevated in protease-defective cells.
pubmed:affiliation
University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Department of Microbiology and Molecular Genetics, International Center for Public Health, Newark, NJ 07101, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural