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| Status |
Public on Sep 15, 2013 |
| Title |
Multiple DNA repair pathways collectively protect against DNA damage-induced replicative aging. |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by array
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| Summary |
We demonstrate that transcriptomic profiling of the NER mutant ercc-1 offers better understanding of the complex phenotypes of ercc-1 deficiency in C. elegans, as it does in mammalian models. There is a transcriptomic shift in ercc-1 mutants that suggests a stochastic impairment of growth and development, with a shift towards a higher proportion of males in the population. Extensive phenotypic analyses confirm that NER deficiency in C. elegans leads to severe developmental and growth defects and a reduced replicative lifespan, although post-mitotic lifespan is not affected. Results suggest that these defects are caused by an inability to cope with randomly occurring DNA damage, which may interfere with transcription and replication.
The study investigates the developmental and aging phenotypes of different NER deficient C. elegans mutants (xpa-1, ercc-1, xpf-1 and xpg-1), where the transcriptomic profile of ercc-1 mutant is presented. We show that loss of NER function does not affect post-mitotic lifespan, but leads to impaired embryogenesis, germ cell and larval development and causes a reduced replicative lifespan. Phenotypes are most pronounced in ercc-1, xpf-1 and xpg-1 mutant animals. We provide evidence that this more pronounced phenotype is likely caused by the fact that these genes are involved in multiple repair pathways besides NER. Furthermore, transcriptional profiling of ercc-1 mutants confirms these observations, showing that growth and developmental pathways are underrepresented but that insulin signaling is not affected. Our analysis suggests that XPA-1, ERCC-1, XPF-1 and XPG-1 protect animals against replicative aging by preventing the accumulation of randomly acquired DNA damage.
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| Overall design |
Eight mixed stage C. elegans samples were run on Affymetrix GeneChip C. elegans Genome Arrays. Four samples belong to ercc-1 mutant group and four to the wild-type, N2.
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| Contributor(s) |
Lans H, Lindvall JM, Thijssen K, Karambelas A, Cupac D, Fensgård A, Jansen G, Hoeijmakers JH, Nilsen H, Vermeulen W |
| Citation(s) |
24013725 |
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| Submission date |
Jul 05, 2012 |
| Last update date |
Jul 06, 2016 |
| Contact name |
Jessica Margareta Lindvall |
| E-mail(s) |
jessica.lindvall@nbis.se
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| Organization name |
SciLifeLab. Stockholm University
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| Department |
NBIS
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| Street address |
Tomtebodavägen 23A
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| City |
Solna |
| ZIP/Postal code |
11111 |
| Country |
Sweden |
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| Platforms (1) |
| GPL200 |
[Celegans] Affymetrix C. elegans Genome Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA170083 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39145_RAW.tar |
16.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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