title: Loss of DNase II function in the gonad is associated with a higher expression of antimicrobial genes in Caenorhabditis elegans.
abstract: Three waves of apoptosis shape the development of Caenorhabditis elegans. Although the exact roles of the three DNase II genes (nuc-1, crn-6 and crn-7), which are known to mediate degradation of apoptotic DNA, in the embryonic and larval phases of apoptosis have been characterized, the DNase II acting in the third wave of germ cell apoptosis remains undetermined. In the present study, we performed in vitro and in vivo assays on various mutant nematodes to demonstrate that NUC-1 and CRN-7, but not CRN-6, function in germ cell apoptosis. In addition, in situ DNA-break detection and anti-phosphorylated ERK (extracellular-signal-regulated kinase) staining illustrated the sequential and spatially regulated actions of NUC-1 and CRN-7, at the pachytene zone of the gonad and at the loop respectively. In line with the notion that UV-induced DNA fragment accumulation in the gonad activates innate immunity responses, we also found that loss of NUC-1 and CRN-7 lead to up-regulation of antimicrobial genes (abf-2, spp-1, nlp-29, cnc-2, and lys-7). Our observations suggest that an incomplete digestion of DNA fragments resulting from the absence of NUC-1 or CRN-7 in the gonad could induce the ERK signalling, consequently activating antimicrobial gene expression. Taken together, the results of the present study demonstrate for the first time that nuc-1 and crn-7 play a role in degrading apoptotic DNA in distinct sites of the gonad, and act as negative regulators of innate immunity in C. elegans.
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
authors.forename: Hsiang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Lai
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333.
authors.forename: Tai-Wei
authors.initials: TW
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan 701 cschen@mail.ncku.edu.tw losj@mail.cgu.edu.tw.
authors.forename: Chang-Shi
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333 cschen@mail.ncku.edu.tw losj@mail.cgu.edu.tw.
authors.forename: Szecheng J
authors.initials: SJ
authors.lastname: Lo
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000502:physiology*; D005786:Gene Expression Regulation; D006066:Gonads / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II
keywords: Caenorhabditis elegans; DNase II; antimicrobial gene; apoptosis; innate immunity