title: Molecular analysis and functions of p53R2 in zebrafish.
abstract: p53R2 is a newly identified small subunit of ribonucleotide reductase and plays a pivotal role in the supply of dNTPs for genomic DNA repair and mitochondrial DNA synthesis, but little is known about its functions in zebrafish. Herein, we obtained the cDNA of zebrafish p53R2 that shares 72.8% and 72.5% amino acid identities with human p53R2 and zebrafish R2, respectively. Residues crucial for enzymatic activity are highly conserved among p53R2 proteins from different species. p53R2 in zebrafish was maternally expressed, its transcripts were detected in developing embryos and all adult tissues examined. A 250-bp minimal promoter upstream of the translational initiation site was identified to drive basal expression of p53R2 in a p53-independent manner. Expression of p53R2 was induced by DNA-damaging reagents CPT or MMS, but suppressed by p53-knockdown in zebrafish embryos. Moreover, p53R2 was mainly distributed in the cytoplasm of cells under normal condition and upon DNA damage. Furthermore, overexpression of p53R2 attenuated apoptosis of embryonic cells caused by CPT or MMS treatment and protected developing embryos from death. Therefore, functions of p53R2 in zebrafish are closely associated with its activity in DNA repair and synthesis.
authors.affiliation: Key Laboratory of Biodiversity and Conservation of Aquatic Organism; Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu Rd., Wuhan, Hubei, PR China.
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Shang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Guohui
authors.initials: G
authors.lastname: Feng
authors.forename: Zongbin
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000201:enzymology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D012264:Ribonucleotide Reductases; C557322:p53R2 protein, zebrafish