dc.contributor.author |
Astin, Jonathan |
en |
dc.contributor.author |
O'Neil, NJ |
en |
dc.contributor.author |
Kuwabara, PE |
en |
dc.coverage.spatial |
Netherlands |
en |
dc.date.accessioned |
2012-01-25T02:02:23Z |
en |
dc.date.issued |
2008-02-01 |
en |
dc.identifier.citation |
DNA Repair 7(2):267-280 01 Feb 2008 |
en |
dc.identifier.issn |
1568-7864 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/10721 |
en |
dc.description.abstract |
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. |
en |
dc.language |
eng |
en |
dc.publisher |
Elsevier B.V. |
en |
dc.relation.ispartofseries |
DNA Repair |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1568-7864/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Animals |
en |
dc.subject |
Base Sequence |
en |
dc.subject |
Blotting, Western |
en |
dc.subject |
Caenorhabditis elegans |
en |
dc.subject |
Caenorhabditis elegans Proteins |
en |
dc.subject |
DNA Repair |
en |
dc.subject |
Gene Components |
en |
dc.subject |
Longevity |
en |
dc.subject |
Molecular Sequence Data |
en |
dc.subject |
Oligonucleotides |
en |
dc.subject |
Paraquat |
en |
dc.subject |
RNA Interference |
en |
dc.subject |
RNA Polymerase II |
en |
dc.subject |
Reverse Transcriptase Polymerase Chain Reaction |
en |
dc.subject |
Sequence Analysis, DNA |
en |
dc.subject |
Transcription, Genetic |
en |
dc.subject |
Ubiquitin-Protein Ligases |
en |
dc.subject |
Ultraviolet Rays |
en |
dc.subject |
Xeroderma Pigmentosum Group A Protein |
en |
dc.title |
Nucleotide excision repair and the degradation of RNA pol II by the Caenorhabditis elegans XPA and Rsp5 orthologues, RAD-3 and WWP-1. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.dnarep.2007.10.004 |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
267 |
en |
pubs.volume |
7 |
en |
dc.rights.holder |
Copyright: Elsevier B.V. |
en |
dc.identifier.pmid |
18053776 |
en |
pubs.end-page |
280 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
253832 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
dc.identifier.pii |
S1568-7864(07)00353-9 |
en |
pubs.record-created-at-source-date |
2012-01-26 |
en |
pubs.dimensions-id |
18053776 |
en |