Bruno Robert de Saint Vincent

Publications (3)12.52 Total impact

• Source

  Available from: Marcin Feder

  Article: Characterization of prmt7alpha and beta isozymes from Chinese hamster cells sensitive and resistant to topoisomerase II inhibitors.

  Laurent Gros, Axelle Renodon-Cornière, Bruno Robert de Saint Vincent, Marcin Feder, Janusz M Bujnicki, Alain Jacquemin-Sablon
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  ABSTRACT: By selection of genetic suppressor elements (GSEs) conferring resistance to topoisomerase II inhibitors in Chinese hamster cells (DC-3F), we identified a gene encoding two proteins of 78 and 82 kDa which belong to the protein arginine methyltransferase (PRMT) family. Down-regulation of these enzymes (named PRMT7alpha and beta), either induced by an antisense GSE or as observed in the 9-OH-ellipticine (9-OH-E) resistant mutant DC-3F/9-OH-E, was responsible for cell resistance to various DNA damaging agents. Alternative splicing alterations in the 5'-terminal region and changes of the polyadenylation site of PRMT7 mRNAs were observed in these resistant mutant cells. PRMT7alpha and beta are isoforms of a highly conserved protein containing two copies of a module common to all PRMTs, comprising a Rossmann-fold domain and a beta-barrel domain. The C-terminal repeat appears to be degenerate and catalytically inactive. PRMT7alpha and beta form homo- and hetero-dimers but differ by their sub-cellular localization and in vitro recognize different substrates. PRMT7beta was only observed in Chinese hamster cells while mouse 10T1/2 fibroblasts only contain PRMT7alpha. Surprisingly, in human cells the anti-PRMT7 antibody essentially recognized an approximately 37 kDa peptide, which is not formed during extraction, and a faint band at 78 kDa. Analysis of in vitro and in vivo methylation patterns in cell lines under- or over-expressing PRMT7alpha and beta detected a discrete number of proteins which methylation and/or expression are under the control of these enzymes.
  Biochimica et Biophysica Acta 12/2006; 1760(11):1646-56. · 4.66 Impact Factor
• Article: Identification of new drug sensitivity genes using genetic suppressor elements: protein arginine N-methyltransferase mediates cell sensitivity to DNA-damaging agents.

  Laurent Gros, Charlotte Delaporte, Stéphane Frey, Julien Decesse, Bruno Robert de Saint-Vincent, Laurent Cavarec, Anne Dubart, Andrei V Gudkov, Alain Jacquemin-Sablon
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  ABSTRACT: Genetic suppressor elements (GSEs) are cDNA fragments encoding either truncated proteins, acting as dominant-negative mutants, or inhibitory antisense RNA segments counteracting with the gene from which they are derived. To identify genes controlling the cell response to cytotoxic agents, a normalized retroviral library of randomly fragmented cDNAs from Chinese hamster cell line DC-3F was screened for GSEs conferring resistance to the topoisomerase II inhibitor 9-OH-ellipticine. From 218 cDNA fragments isolated, 11 functional GSEs, corresponding to at least 8 independent genes, were selected. The gene corresponding to the most abundant GSE encodes two proteins, p77 and p82, highly homologous to proteins detected in various species and carrying the sequence motifs characteristic of the protein arginine N-methyltransferase family. Furthermore, a methylase activity was observed on myelin basic protein in immunoprecipitates of hemagglutinin-tagged p77 and p82. Therefore, p77 and p82 are the first identified members of a new protein arginine N-methyltransferase family. A decreased expression of these enzymes is associated with either resistance or hypersensitivity to a broad range of DNA-damaging agents. Our data indicate that down-regulation of these enzymes in the GSE-expressing cells would alter one or several steps downstream of the drug-target interaction in the drug-response pathway.
  Cancer Research 02/2003; 63(1):164-71. · 7.86 Impact Factor
• Article: Characterization of prmt7α and β isozymes from Chinese hamster cells sensitive and resistant to topoisomerase II inhibitors

  Laurent Gros, Axelle Renodon-Cornière, Bruno Robert de Saint Vincent, Marcin Feder, Janusz M. Bujnicki, Alain Jacquemin-Sablon
  [show abstract] [hide abstract]
  ABSTRACT: By selection of genetic suppressor elements (GSEs) conferring resistance to topoisomerase II inhibitors in Chinese hamster cells (DC-3F), we identified a gene encoding two proteins of 78 and 82 kDa which belong to the protein arginine methyltransferase (PRMT) family. Down-regulation of these enzymes (named PRMT7α and β), either induced by an antisense GSE or as observed in the 9-OH-ellipticine (9-OH-E) resistant mutant DC-3F/9-OH-E, was responsible for cell resistance to various DNA damaging agents. Alternative splicing alterations in the 5'-terminal region and changes of the polyadenylation site of PRMT7 mRNAs were observed in these resistant mutant cells. PRMT7α and β are isoforms of a highly conserved protein containing two copies of a module common to all PRMTs, comprising a Rossmann-fold domain and a β-barrel domain. The C-terminal repeat appears to be degenerate and catalytically inactive. PRMT7α and β form homo- and hetero-dimers but differ by their sub-cellular localization and in vitro recognize different substrates. PRMT7β was only observed in Chinese hamster cells while mouse 10T1/2 fibroblasts only contain PRMT7α. Surprisingly, in human cells the anti-PRMT7 antibody essentially recognized an ∼ 37 kDa peptide, which is not formed during extraction, and a faint band at 78 kDa. Analysis of in vitro and in vivo methylation patterns in cell lines under- or over-expressing PRMT7α and β detected a discrete number of proteins which methylation and/or expression are under the control of these enzymes.
  Biochimica et Biophysica Acta (BBA) - General Subjects.