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Cuts can kill: the roles of apoptotic nucleases in cell death and animal development

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Abstract

Chromosome fragmentation is one of the major biochemical hallmarks of apoptosis. However, until recently, its roles in apoptosis and mechanisms of action remained elusive. Recent biochemical and genetic studies have shown that chromosome fragmentation is a complex biochemical process that involves a plethora of conserved nucleases with distinct nuclease activities and substrate specificities. These apoptotic nucleases act cooperatively among themselves and with other nonnuclease cofactors to promote stepwise chromosome fragmentation and DNA degradation. Importantly, in addition to its direct contribution to the dismantling of the dying cell, apoptotic DNA degradation can facilitate cell killing and other apoptotic events such as clearance of apoptotic cells. Furthermore, some apoptotic nucleases apparently affect other aspects of animal development, including immune responses. The identification of new apoptotic nucleases and analysis of their functions in apoptosis and animal development should pave the way for future studies to uncover new functions for apoptotic nucleases and shed light on the hidden links between apoptotic DNA degradation and human diseases.

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Acknowledgements

J.P. was supported by a National Science foundation (NSF) graduate research fellowship. D.X. was supported by a Burroughs Wellcome Fund Career Award, a Searle Scholar Award, and research grants from the National Institutes of Health (NIH) and Department of Defense.

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  1. Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA

    Jay Z. Parrish & Ding Xue

  2. Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California San Francisco, Room GD481, 1550 4th St., Rock Hall, San Francisco, CA, 94143, USA

    Jay Z. Parrish

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  1. Jay Z. Parrish
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Correspondence to Ding Xue.

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Communicated by E.A. Nigg

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Parrish, J.Z., Xue, D. Cuts can kill: the roles of apoptotic nucleases in cell death and animal development. Chromosoma 115, 89–97 (2006). https://doi.org/10.1007/s00412-005-0038-0

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