title: Characterization of prmt7alpha and beta isozymes from Chinese hamster cells sensitive and resistant to topoisomerase II inhibitors.
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.
authors.affiliation: CNRS FRE2618, Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gros
authors.forename: Axelle
authors.initials: A
authors.lastname: Renodon-Cornière
authors.forename: Bruno Robert
authors.initials: BR
authors.lastname: de Saint Vincent
authors.forename: Marcin
authors.initials: M
authors.lastname: Feder
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquemin-Sablon
mesh_terms: D000818:Animals; D002453:Cell Cycle; D006224:Cricetinae; D003412:Cricetulus; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics; D051379:Mice; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D059005:Topoisomerase II Inhibitors; D008780:Methyltransferases; C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases; D004250:DNA Topoisomerases, Type II