Figure 1.-The
mcd-1 Zn finger and
dpl-1 DP genes were identified as cell death-promoting genes from a genetic screen. (A)Ventral cord cell lineage diagrams. W, W blast cell. P, P blast cell. Arrows, cells that fail to die and that express Plin-11 gfp. In the wildtype, P3-8.aap (a, anterior daughter; p, posterior daughter) survive and express Plin-11 gfp. W.ap, P1-2.aap, and P9-12.aap normallydie (Sulston and Horvitz 1977). In
ced-3(lf) animals, no cell death occurs and W.ap, P1-2.aap, and P-12.aap survive and expressPlin-11 gfp (Reddien et al. 2001). The large green midbody region reflects GFP expression in the vulva from the
lin-11 promoter. (B)Schematic of the
ced-3(
n2427) enhancer screen (see text for details). (C) Results from the
ced-3 enhancer screen. From 13,000mutagenized haploid genomes, 37 mutations were isolated. (D and E) Distribution of percentages of animals with zero to fiveextra cells in the ventral cord. The five cells P2.aap and P9-12.aap were scored using the assay described. At least 50 young adultanimals of each genotype were scored. nIs106, Plin-11 gfp reporter (Reddien et al. 2001). (F)
n3380 is located in the region on LGIIbetween the genes
rol-6 and
unc-4.
n3376 is located between two polymorphisms, nP89 and nP91, on LGII, a region of 75 kb. Seematerials and methods for details. (G) Protein structure of DPL-1 DP. The blue box indicates the putative DNA-binding regionof DPL-1 and the yellow box the putative E2F-binding region, as previously described (Ceol and Horvitz 2001). The
n3316 mutation is a deletion following the third codon, and
n2994 is a splice-site mutation predicted to alter protein structure followingamino acid 227 (Ceol and Horvitz 2001).
n3380 is a C-to-T nonsense mutation that is at Q486. (H) The gene Y51H1A.6 is
mcd-1 (see text for details). The 59 end carries an SL1 trans-spliced leader sequence (see text), and the 39-UTR is 750 bp. We isolated adeletion allele,
n4005, that removes part of intron two and part of exon three of Y51H1A.6 (see materials and methods). Thered line labeled ''Zn'' depicts the zinc-finger-encoding region of
mcd-1. The MCD-1 zinc-finger region amino acid sequence isshown below the gene structure diagram. Red stars indicate the residues that define the C2H2 domain, and blue stars indicateother residues conserved with the canonical C2H2 zinc finger.
n3376 is a C-to-T mutation resulting in an H277Y substitution in theMCD-1 protein and is indicated by a red arrowhead.