53BP1 Oligomerization is Independent of its Methylation by PRMT1

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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 thebiochemical functions of 53BP1, the protein possesses several motifs that are likely important for itsrole as a DNA damage response element. This includes two BRCA1 C-terminal repeats, tandemTudor 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 thatarginine residues within this region are important for asymmetric methylation by the PRMT1methyltransferase. We further show that sequences upstream of the Tudor domains that do notinclude the GAR stretch are sufficient for 53BP1 oligomerization in vivo. Thus, although Tudordomains bind methylated proteins, 53BP1 homo-oligomerization occurs independently of Tudorfunction. 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 genomicstability.

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