title: Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism.
abstract: Proteins of the metallo-beta-lactamase family with either demonstrated or predicted nuclease activity have been identified in a number of organisms ranging from bacteria to humans and has been shown to be important constituents of cellular metabolism. Nucleases of this family are believed to utilize a zinc-dependent mechanism in catalysis and function as 5' to 3' exonucleases and or endonucleases in such processes as 3' end processing of RNA precursors, DNA repair, V(D)J recombination, and telomere maintenance. Examples of metallo-beta-lactamase nucleases include CPSF-73, a known component of the cleavage/polyadenylation machinery, which functions as the endonuclease in 3' end formation of both polyadenylated and histone mRNAs, and Artemis that opens DNA hairpins during V(D)J recombination. Mutations in two metallo-beta-lactamase nucleases have been implicated in human diseases: tRNase Z required for 3' processing of tRNA precursors has been linked to the familial form of prostate cancer, whereas inactivation of Artemis causes severe combined immunodeficiency (SCID). There is also a group of as yet uncharacterized proteins of this family in bacteria and archaea that based on sequence similarity to CPSF-73 are predicted to function as nucleases in RNA metabolism. This article reviews the cellular roles of nucleases of the metallo-beta-lactamase family and the recent advances in studying these proteins.
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. dominski@med.unc.edu
authors: Zbigniew
authors: Z
authors: Dominski
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D039223:Cleavage And Polyadenylation Specificity Factor / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D039223:Cleavage And Polyadenylation Specificity Factor; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D008667:Metalloproteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D012342:RNA, Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D004247:DNA; C426344:DCLRE1C protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D004722:Endoribonucleases; C090162:PSO2 protein, S cerevisiae; C502293:tRNase Z, Drosophila; D001618:beta-Lactamases