Abstract
Chromosomal DNA degradation is critical for cell death execution and is a hallmark of apoptosis, yet little is known about how this process is executed. Using an RNAi-based functional genomic approach, we have identified seven additional cell death-related nucleases (crn genes), which along with two known nucleases (CPS-6 and NUC-1) comprise at least two independent pathways that contribute to cell killing, and likely signaling for phagocytosis, by degrading chromosomal DNA. Several crn genes have human homologs that are important for RNA processing, protein folding, DNA replication, and DNA damage repair, suggesting dual roles for CRN nucleases in cell survival and cell death. It should now be possible to systematically decipher the mechanisms of apoptotic DNA degradation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / genetics
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Animals
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Apoptosis / genetics*
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Base Sequence / genetics
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Cells, Cultured
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DNA / genetics*
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Deoxyribonucleases / genetics
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Deoxyribonucleases / isolation & purification*
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Embryo, Nonmammalian
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Endodeoxyribonucleases / genetics
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Endodeoxyribonucleases / metabolism
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Genome*
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Molecular Sequence Data
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Phagocytosis / genetics
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RNA, Small Interfering
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Signal Transduction / genetics
Substances
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Caenorhabditis elegans Proteins
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Cps-6 protein, C elegans
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Mitochondrial Proteins
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RNA, Small Interfering
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DNA
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Deoxyribonucleases
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Endodeoxyribonucleases
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deoxyribonuclease II