{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:15:25Z","timestamp":1791350125363,"version":"4.3.1"},"reference-count":37,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5542","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,10,19]]},"abstract":"<jats:p>\n                    We have identified a homolog of the mammalian p53 tumor suppressor protein in the nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    that is expressed ubiquitously in embryos. The gene encoding this protein,\n                    <jats:italic>cep-1<\/jats:italic>\n                    , promotes DNA damage\u2013induced apoptosis and is required for normal meiotic chromosome segregation in the germ line. Moreover, although somatic apoptosis is unaffected,\n                    <jats:italic>cep-1<\/jats:italic>\n                    mutants show hypersensitivity to hypoxia-induced lethality and decreased longevity in response to starvation-induced stress. Overexpression of CEP-1 promotes widespread caspase-independent cell death, demonstrating the critical importance of regulating p53 function at appropriate levels. These findings show that\n                    <jats:italic>C. elegans<\/jats:italic>\n                    p53 mediates multiple stress responses in the soma, and mediates apoptosis and meiotic chromosome segregation in the germ line.\n                  <\/jats:p>","DOI":"10.1126\/science.1065486","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:54:32Z","timestamp":1027749272000},"page":"591-595","source":"Crossref","is-referenced-by-count":418,"title":["<i>Caenorhabditis elegans<\/i>\n                    p53: Role in Apoptosis, Meiosis, and Stress Resistance"],"prefix":"10.1126","volume":"294","author":[{"given":"W. Brent","family":"Derry","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Putzke","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81871-1"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.9.1054"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80626-1"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80627-3"},{"key":"e_1_3_1_6_2","unstructured":"S. Jin et al. Proc. Natl. Acad. Sci. U.S.A. 97 7301 (2000)."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5461.2204"},{"key":"e_1_3_1_8_2","unstructured":"The amino acid sequence of squid ( Loligo forbesi ) p53 (U43595) was used as a query to search the C. elegans database with the PSI-BLAST algorithm (25). Several low-scoring C. elegans open reading frames were identified and aligned with several p53 family members using the Block Maker tool (26). F52B5.5 was the only predicted C. elegans gene identified with the appropriate p53 signature sequences in the correct modular order. There are seven exons in cep-1 and the intron-exon boundaries are in similar positions to those in the murine and human p53 genes (27 28) underscoring their evolutionary relatedness."},{"key":"e_1_3_1_9_2","unstructured":"We screened 48 000 wild-type (N2) genomes for a cep-1 deletion using 4 5\u2032 8-trimethylpsoralen\/ultraviolet light mutagenesis as described (29 30). First-round polymerase chain reaction primers flanking cep-1 were 5\u2032-GGTGGACTGTTGCTTTGAAATCAAGACTGC-3\u2032 and 5\u2032-GCTCTTGATGTTGCCAACAAGATCGGATTC-3\u2032. Second-round primers were 5\u2032-CAGGGGAGTTGGCGTTAGG-3\u2032 and 5\u2032-AATTGGTACAGCGACTTCTCTTCA-3\u2032. A single worm containing the cep-1(w40) deletion was identified. This deletion removes 1823 nucleotides of the gene corresponding to nucleotides 28 754 to 31 967 on cosmid F52B5. The splice acceptor and donor sites remain intact in the cep-1(w40) allele which is predicted to encode an in-frame but truncated protein missing amino acids 69 to 242. Further analysis showed that the deletion strain also carries an intact copy of cep-1. The w40 allele segregates independently of the wild-type cep-1 locus indicating that the deleted copy had translocated to another region of the genome and a wild-type copy of cep-1 remains at the normal locus."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","unstructured":"A. Fire et al. Nature 391 806 (1998).","DOI":"10.1038\/35888"},{"key":"e_1_3_1_11_2","unstructured":"W. B. Derry J. H. Rothman unpublished data."},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80438-4"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.5.1011"},{"key":"e_1_3_1_14_2","unstructured":"D. G. Albertson A. M. Rose A. M. Villeneuve in C. elegans II D. L. Riddle T. Blumenthal B. J. Meyer J. R. Priess Eds. (Cold Spring Harbor Laboratory Press Cold Spring Harbor NY 1997) pp. 47\u201378."},{"key":"e_1_3_1_15_2","unstructured":"To determine the expression pattern of cep-1 we designed a reporter construct that includes 4.5 kb of sequence upstream of the start codon as well as the entire CEP-1 coding sequence fused in-frame to GFP. The cep-1 sequences were obtained by amplification from cosmid F52B5 and cloned into vector pPD 96.04. Reporter constructs were coinjected with the dominant rol-6(su1006) marker gene to create transgenic lines (31). This results in repetitive arrays that are generally silenced in the germ line; thus the marker is likely to reveal the zygotic expression exclusively."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"T. Jacks et al. Curr. Biol. 4 1 (1994).","DOI":"10.1353\/mod.1994.0050"},{"key":"e_1_3_1_17_2","first-page":"2851","volume":"5","author":"Rogel A.","year":"1985","unstructured":"Rogel A., Popliker M., Webb C. G., Oren M., Mol. Cell. Biol. 5, 2851 (1985).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.3.857"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","unstructured":"J. B. Wallingford D. W. Seufert V. C. Virta P. D. Vize Curr. Biol. 7 747 (1997).","DOI":"10.1016\/S0960-9822(06)00333-2"},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","unstructured":"T. G. Graeber et al. Mol. Cell. Biol. 14 6264 (1994).","DOI":"10.1128\/mcb.14.9.6264-6277.1994"},{"key":"e_1_3_1_21_2","first-page":"6046","volume":"59","author":"Alarc\u00f3n R.","year":"1999","unstructured":"Alarc\u00f3n R., Koumenis C., Geyer R. K., Maki C. G., Giaccia A. J., Cancer Res. 59, 6046 (1999).","journal-title":"Cancer Res."},{"key":"e_1_3_1_22_2","unstructured":"Genomic cep-1 was amplified from cosmid F52B5 using primers tagged with a Kpn I site 5\u2032 of the ATG start codon and a Sac I site after the stop codon and cloned into vectors pPD 49.78 ( hsp16-2 ) and pPD 49.83 ( hsp16-41 ). Transgenic lines were established by standard methods (31). The primers were 5\u2032-GCGGTACCATGAATTTGAATGAAGATTG-3\u2032 and 5\u2032-CCGAGCTCTTACTTTGGCAGTTTCATCG-3\u2032. CEP-1 was overexpressed in transgenic worms by subjecting them to a 15- to 20-min heat shock at 34\u00b0C (32)."},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90004-8"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117.1.29"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400526"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00486-P"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1984.tb02110.x"},{"key":"e_1_3_1_29_2","first-page":"1379","volume":"6","author":"Lamb P.","year":"1986","unstructured":"Lamb P., Crawford L., Mol. Cell. Biol. 6, 1379 (1986).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-119"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2260"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04966.x"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.2.221"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1626"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8023157"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.10.1235"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7809597"},{"key":"e_1_3_1_38_2","unstructured":"We thank M. Fukuyama for help with the deletion screen C. Farmer and the Tri-Counties Blood Bank for use of their gamma source R. Christoffersen for hypoxic chambers S. Roberts for providing the three-dimensional model R. Halberg for useful discussions A. Fire for vectors and A. Coulson for cosmids. Some of the strains were provided by the Caenorhabditis Genetics Center which is funded by the National Center for Research Resources of NIH. Supported by the Cancer Center of Santa Barbara and the Tri-Counties Blood Bank (W.B.D.) and grants from Santa Barbara Cottage Hospital the University of California Cancer Research Coordinating Committee and National Institute on Aging grant AG13736 (J.H.R.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1065486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T14:38:31Z","timestamp":1733668711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1065486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,10,19]]},"references-count":37,"journal-issue":{"issue":"5542","published-print":{"date-parts":[[2001,10,19]]}},"alternative-id":["10.1126\/science.1065486"],"URL":"https:\/\/doi.org\/10.1126\/science.1065486","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1004162.17107","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1004162.19904","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1004162.15857","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1004162.7724","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1004162.7754","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,10,19]]}}}