RRC ID 46709
Author Nakagawa A, Shi Y, Kage-Nakadai E, Mitani S, Xue D.
Title Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.
Journal Science
Abstract Chromosome fragmentation is a hallmark of apoptosis, conserved in diverse organisms. In mammals, caspases activate apoptotic chromosome fragmentation by cleaving and inactivating an apoptotic nuclease inhibitor. We report that inactivation of the Caenorhabditis elegans dcr-1 gene, which encodes the Dicer ribonuclease important for processing of small RNAs, compromises apoptosis and blocks apoptotic chromosome fragmentation. DCR-1 was cleaved by the CED-3 caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3' hydroxyl DNA breaks on chromosomes and promoted apoptosis. Thus, caspase-mediated activation of apoptotic DNA degradation is conserved. DCR-1 functions in fragmenting chromosomal DNA during apoptosis, in addition to processing of small RNAs, and undergoes a protease-mediated conversion from a ribonuclease to a deoxyribonuclease.
Volume 328(5976)
Pages 327-34
Published 2010-4-16
DOI 10.1126/science.1182374
PII science.1182374
PMID 20223951
PMC PMC4313557
MeSH Animals Animals, Genetically Modified Apoptosis* Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caspases / genetics Caspases / metabolism* Catalytic Domain DNA Fragmentation* DNA, Helminth / metabolism* Deoxyribonucleases / metabolism* In Situ Nick-End Labeling RNA Interference RNA, Double-Stranded / metabolism RNA, Helminth / metabolism Recombinant Fusion Proteins / metabolism Ribonuclease III / chemistry Ribonuclease III / genetics Ribonuclease III / metabolism*
IF 41.846
Times Cited 85
C.elegans tm1177 tm1217 tm1496 tm1329