Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.
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.
Nakagawa
Akihisa
A
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Shi
Yong
Y
Kage-Nakadai
Eriko
E
Mitani
Shohei
S
Xue
Ding
D
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D053938:DNA Fragmentation; D018509:DNA, Helminth / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D018510:RNA, Helminth / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D012330:RNA, Double-Stranded; D018510:RNA, Helminth; D011993:Recombinant Fusion Proteins; D003851:Deoxyribonucleases; C118116:dcr-1 protein, C elegans; D043244:Ribonuclease III; D020169:Caspases; C089223:ced-3 protein, C elegans