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Abstract
Programmed cell death (or apoptosis) is an evolutionarily conserved, genetically controlled suicide mechanism for cells that, when deregulated, can lead to developmental defects, cancers, and degenerative diseases [1, 2]. In C. elegans, DNA damage induces germ cell death by signaling through cep-1/p53, ultimately leading to the activation of CED-3/caspase [3-13]. It has been hypothesized that the major regulatory events controlling cell death occur by cell-autonomous mechanisms, that is, within the dying cell. In support of this, genetic studies in C. elegans have shown that the core apoptosis pathway genes ced-4l APAF-1 and ced-3/caspase are required in cells fated to die [9]. However, it is not known whether the upstream signals that activate apoptosis function in a cell-autonomous manner. Here we show that kri-1, an ortholog of KRIT1/CCM1, which is mutated in the human neurovascular disease cerebral cavernous malformation [14, 15], is required to activate DNA damage-dependent cell death independently of cep-1/p53. Interestingly, we find that kri-1 regulates cell death in a cell-nonautonomous manner, revealing a novel regulatory role for nondying cells in eliciting cell death in response to DNA damage.
Original language | English |
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Pages (from-to) | 333-338 |
Number of pages | 6 |
Journal | Current Biology |
Volume | 20 |
Issue number | 4 |
DOIs | |
Publication status | Published - 23 Feb 2010 |
Keywords
- DAMAGE-INDUCED APOPTOSIS
- DNA-DAMAGE
- CAENORHABDITIS-ELEGANS
- CHECKPOINT PROTEIN
- LIFE-SPAN
- TUMOR-SUPPRESSOR
- ENCODING KRIT1
- GENE
- CED-4
- P53
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Dive into the research topics of 'Cell-Nonautonomous Regulation of C. elegans Germ Cell Death by kri-1'. Together they form a unique fingerprint.Projects
- 1 Finished
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Combined Genetic and Biochemical Approaches to Uncover and Characterize Redundant Factors Involved in Late Stages of Recombinational Repair
Gartner, A. (Investigator) & Lamond, A. (Investigator)
1/08/10 → 30/04/17
Project: Research