Linked Life Data

18053776

Source:http://linkedlifedata.com/resource/pubmed/id/18053776

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-7
pubmed:abstractText
The Caenorhabditis elegans rad-3 gene was identified in a genetic screen for radiation sensitive (rad) mutants. Here, we report that the UV sensitivity of rad-3 mutants is caused by a nonsense mutation in the C. elegans orthologue of the human nucleotide excision repair gene XPA. We have used the xpa-1/rad-3 mutant to examine how a defect in nucleotide excision repair (NER) perturbs development. We find that C. elegans carrying a mutation in xpa-1/rad-3 are hypersensitive and hypermutable in response to UV irradiation, but do not display hypersensitivity to oxidative stress or show obvious developmental abnormalities in the absence of UV exposure. Consistent with these observations, non-irradiated xpa-1 mutants have a similar lifespan as wild type. We further show that UV irradiated xpa-1 mutants undergo a stage-dependent decline in growth and survival, which is associated with a loss in transcriptional competence. Surprisingly, transcriptionally quiescent dauer stage larvae are able to survive a dose of UV irradiation, which is otherwise lethal to early stage larvae. We show that the loss of transcriptional competence in UV irradiated xpa-1 mutants is associated with the degradation of the large RNA polymerase II (RNA pol II) subunit, AMA-1, and have identified WWP-1 as the putative E3 ubiquitin ligase mediating this process. The absence of wwp-1 by itself does not cause sensitivity to UV irradiation, but it acts synergistically with a mutation in xpa-1 to enhance UV hypersensitivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1568-7864
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-80
pubmed:meshHeading
pubmed-meshheading:18053776-Animals, pubmed-meshheading:18053776-Base Sequence, pubmed-meshheading:18053776-Blotting, Western, pubmed-meshheading:18053776-Caenorhabditis elegans, pubmed-meshheading:18053776-Caenorhabditis elegans Proteins, pubmed-meshheading:18053776-DNA Repair, pubmed-meshheading:18053776-Gene Components, pubmed-meshheading:18053776-Longevity, pubmed-meshheading:18053776-Molecular Sequence Data, pubmed-meshheading:18053776-Oligonucleotides, pubmed-meshheading:18053776-Paraquat, pubmed-meshheading:18053776-RNA Interference, pubmed-meshheading:18053776-RNA Polymerase II, pubmed-meshheading:18053776-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18053776-Sequence Analysis, DNA, pubmed-meshheading:18053776-Transcription, Genetic, pubmed-meshheading:18053776-Ubiquitin-Protein Ligases, pubmed-meshheading:18053776-Ultraviolet Rays, pubmed-meshheading:18053776-Xeroderma Pigmentosum Group A Protein
pubmed:year
2008
pubmed:articleTitle
Nucleotide excision repair and the degradation of RNA pol II by the Caenorhabditis elegans XPA and Rsp5 orthologues, RAD-3 and WWP-1.
pubmed:affiliation
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural