title: PRMT1 arginine methyltransferase accumulates in cytoplasmic bodies that respond to selective inhibition and DNA damage.
abstract: Protein arginine methyltransferases (PRMTs) are responsible for symmetric and asymmetric methylation of arginine residues of nuclear and cytoplasmic proteins. In the nucleus, PRMTs belong to important chromatin modifying enzymes of immense functional significance that affect gene expression, splicing and DNA repair. By time-lapse microscopy we have studied the sub-cellular localization and kinetics of PRMT1 after inhibition of PRMT1 and after irradiation. Both transiently expressed and endogenous PRMT1 accumulated in cytoplasmic bodies that were located in the proximity of the cell nucleus. The shape and number of these bodies were stable in untreated cells. However, when cell nuclei were microirradiated by UV-A, the mobility of PRMT1 cytoplasmic bodies increased, size was reduced, and disappeared within approximately 20 min. The same response occurred after γ-irradiation of the whole cell population, but with delayed kinetics. Treatment with PRMT1 inhibitors induced disintegration of these PRMT1 cytoplasmic bodies and prevented formation of 53BP1 nuclear bodies (NBs) that play a role during DNA damage repair. The formation of 53BP1 NBs was not influenced by PRMT1 overexpression. Taken together, we show that PRMT1 concentrates in cytoplasmic bodies, which respond to DNA injury in the cell nucleus, and to treatment with various PRMT1 inhibitors.
authors.affiliation: Academy of Sciences of the Czech Republic. suchankova.jana@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Suchánková
authors.forename: S
authors.initials: S
authors.lastname: Legartová
authors.forename: P
authors.initials: P
authors.lastname: Sehnalová
authors.forename: S
authors.initials: S
authors.lastname: Kozubek
authors.forename: S
authors.initials: S
authors.lastname: Valente
authors.forename: D
authors.initials: D
authors.lastname: Labella
authors.forename: A
authors.initials: A
authors.lastname: Mai
authors.forename: C
authors.initials: C
authors.lastname: Eckerich
authors.forename: F O
authors.initials: FO
authors.lastname: Fackelmayer
authors.forename: D V
authors.initials: DV
authors.lastname: Sorokin
authors.forename: E
authors.initials: E
authors.lastname: Bartova
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1; D014466:Ultraviolet Rays
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C498301:TP53BP1 protein, human; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1; C099988:PRMT1 protein, human; C546338:Prmt1 protein, mouse; D011484:Protein-Arginine N-Methyltransferases