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.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Akihisa
A
Nakagawa
Yong
Y
Shi
Eriko
E
Kage-Nakadai
Shohei
S
Mitani
Ding
D
Xue
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