RRC ID 6453
Author Lai HJ, Lo SJ, Kage-Nakadai E, Mitani S, Xue D.
Title The roles and acting mechanism of Caenorhabditis elegans DNase II genes in apoptotic dna degradation and development.
Journal PLoS One
Abstract DNase II enzymes are acidic endonucleases that have been implicated in mediating apoptotic DNA degradation, a critical cell death execution event. C. elegans genome contains three DNase II homologues, NUC-1, CRN-6, and CRN-7, but their expression patterns, acting sites, and roles in apoptotic DNA degradation and development are unclear. We have conducted a comprehensive analysis of three C. elegans DNase II genes and found that nuc-1 plays a major role, crn-6 plays an auxiliary role, and crn-7 plays a negligible role in resolving 3' OH DNA breaks generated in apoptotic cells. Promoter swapping experiments suggest that crn-6 but not crn-7 can partially substitute for nuc-1 in mediating apoptotic DNA degradation and both fail to replace nuc-1 in degrading bacterial DNA in intestine. Despite of their restricted and largely non-overlapping expression patterns, both CRN-6 and NUC-1 can mediate apoptotic DNA degradation in many cells, suggesting that they are likely secreted nucleases that are retaken up by other cells to exert DNA degradation functions. Removal or disruption of NUC-1 secretion signal eliminates NUC-1's ability to mediate DNA degradation across its expression border. Furthermore, blocking cell corpse engulfment does not affect apoptotic DNA degradation mediated by nuc-1, suggesting that NUC-1 acts in apoptotic cells rather than in phagocytes to resolve 3' OH DNA breaks. Our study illustrates how multiple DNase II nucleases play differential roles in apoptotic DNA degradation and development and reveals an unexpected mode of DNase II action in mediating DNA degradation.
Volume 4(10)
Pages e7348
Published 2009-10-7
DOI 10.1371/journal.pone.0007348
PMID 19809494
PMC PMC2752799
MeSH Animals Animals, Genetically Modified Apoptosis* Caenorhabditis elegans / physiology* DNA / chemistry DNA Damage Deoxyribonucleases / metabolism Endodeoxyribonucleases / chemistry* Endodeoxyribonucleases / metabolism Endodeoxyribonucleases / physiology* Gene Expression Regulation* Genome Green Fluorescent Proteins / metabolism Intestinal Mucosa / metabolism Kinetics Phagocytes / metabolism
IF 2.74
C.elegans tm890