title: 53BP1 oligomerization is independent of its methylation by PRMT1.
abstract: p53 binding protein 1 (53BP1) participates in the repair of DNA double stranded breaks (DSBs) where it is recruited to or near sites of DNA damage. Although little is known about the biochemical functions of 53BP1, the protein possesses several motifs that are likely important for its role as a DNA damage response element. This includes two BRCA1 C-terminal repeats, tandem Tudor domains, and a variety of phosphorylation sites. Here we show that a glycine-arginine rich (GAR) stretch of 53BP1 lying upstream of the Tudor motifs is methylated. We demonstrate that arginine residues within this region are important for asymmetric methylation by the PRMT1 methyltransferase. We further show that sequences upstream of the Tudor domains that do not include the GAR stretch are sufficient for 53BP1 oligomerization in vivo. Thus, although Tudor domains bind methylated proteins, 53BP1 homo-oligomerization occurs independently of Tudor function. Lastly, we find that deficiencies in 53BP1 generate a "hyper-rec" phenotype. Collectively, these data provide new insight into 53BP1, an important component in maintaining genomic stability.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Adams
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Xia
authors.forename: Julio C
authors.initials: JC
authors.lastname: Morales
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bochar
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Carpenter
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D001704:Biopolymers / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D005998:Glycine / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D001704:Biopolymers; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D005998:Glycine