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Science 328 (5976): 327-334

Copyright © 2010 by the American Association for the Advancement of Science

Caspase-Dependent Conversion of Dicer Ribonuclease into a Death-Promoting Deoxyribonuclease

Akihisa Nakagawa,1,* Yong Shi,1,* Eriko Kage-Nakadai,2 Shohei Mitani,2 Ding Xue1,{dagger}

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.

1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
2 Department of Physiology, Tokyo Women’s Medical University, School of Medicine, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 162-8666, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ding.xue{at}colorado.edu

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