Methylation of MRE11 regulates its nuclear compartmentalization.
The cellular response to DNA damage includes the orderly recruitment of many protein complexes to DNA lesions. The MRE11-RAD50-NBS1 (MRN) complex is well known to localize early to sites of DNA damage, but the post-translational modifications required to mobilize it to DNA damage sites are poorly understood. Recently, we have shown that MRE11 is arginine methylated in a C-terminal glycine-arginine rich (GAR) domain by protein arginine methyltransferase 1 (PRMT1). Arginine methylation is required for the exonuclease activity of MRE11 and the intra-S phase DNA damage response. Herein, we report that cells treated with methylase inhibitors failed to relocalize MRE11 from PML nuclear bodies to sites of DNA damage and formed few gamma-H2AX foci. We also demonstrate that PRMT1 is a component of PML nuclear bodies where it colocalizes with MRE11.Using cellular fractionation, we demonstrate that methylated MRE11 is predominantly associated with nuclear structures and that MRE11 methylated arginines were required for this association. These results suggest that MRE11 methylation regulates its association with nuclear structures such as PML nuclear bodies and sites of DNA damage.
Boisvert
François-Michel
FM
Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Department of Oncology, McGill University, Montréal, Québec, Canada.
Hendzel
Michael J
MJ
Masson
Jean-Yves
JY
Richard
Stéphane
S
D001120:Arginine / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D045586:Intranuclear Inclusion Bodies; D000076228:MRE11 Homologue Protein; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D012097:Repressor Proteins; D001120:Arginine; D008780:Methyltransferases; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D000076228:MRE11 Homologue Protein