Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

MicroRNA-independent roles of the RNase III enzymes Drosha and Dicer.
T. M. Johanson, A. M. Lew, and M. M. W. Chong (2013)
Open Bio 3, 130144
   Abstract »    Full Text »    PDF »
Reply to Shao et al.
J. U. Igietseme and C. M. Black (2013)
The Journal of Infectious Disease 208, 709-710
   Full Text »    PDF »
Prevention of Chlamydia-Induced Infertility by Inhibition of Local Caspase Activity.
J. U. Igietseme, Y. Omosun, J. Partin, J. Goldstein, Q. He, K. Joseph, D. Ellerson, U. Ansari, F. O. Eko, C. Bandea, et al. (2013)
The Journal of Infectious Disease 207, 1095-1104
   Abstract »    Full Text »    PDF »
Structural Insights into Apoptotic DNA Degradation by CED-3 Protease Suppressor-6 (CPS-6) from Caenorhabditis elegans.
J. L. J. Lin, A. Nakagawa, C. L. Lin, Y.-Y. Hsiao, W.-Z. Yang, Y.-T. Wang, L. G. Doudeva, R. R. Skeen-Gaar, D. Xue, and H. S. Yuan (2012)
J. Biol. Chem. 287, 7110-7120
   Abstract »    Full Text »    PDF »
The RNase III enzyme Dicer is essential for germinal center B-cell formation.
S. Xu, K. Guo, Q. Zeng, J. Huo, and K.-P. Lam (2012)
Blood 119, 767-776
   Abstract »    Full Text »    PDF »
A role for miR-296 in the regulation of lipoapoptosis by targeting PUMA.
S. C. Cazanave, J. L. Mott, N. A. Elmi, S. F. Bronk, H. C. Masuoka, M. R. Charlton, and G. J. Gores (2011)
J. Lipid Res. 52, 1517-1525
   Abstract »    Full Text »    PDF »
Dicer's Cut and Switch.
Q. Liu and Z. Paroo (2010)
Science 328, 314-315
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882