Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control.
The role of protein arginine methylation in the DNA damage checkpoint response and DNA repair is largely unknown. Herein we show that the MRE11 checkpoint protein is arginine methylated by PRMT1. Mutation of the arginines within MRE11 severely impaired the exonuclease activity of MRE11 but did not influence its ability to form complexes with RAD50 and NBS1. Cells containing hypomethylated MRE11 displayed intra-S-phase DNA damage checkpoint defects that were significantly rescued with the MRE11-RAD50-NBS1 complex. Our results suggest that arginine methylation regulates the activity of MRE11-RAD50-NBS1 complex during the intra-S-phase DNA damage checkpoint response.
Boisvert
François-Michel
FM
Terry Fox Molecular Oncology Group, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, Québec H3T 1E2, Canada.
Déry
Ugo
U
Masson
Jean-Yves
JY
Richard
Stéphane
S
D017766:Acid Anhydride Hydrolases; D001120:Arginine / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D004249:DNA Damage / Q000235:genetics* / Q000502:physiology; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005982:Glutathione Transferase; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D000076228:MRE11 Homologue Protein; D013058:Mass Spectrometry; D008745:Methylation; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D016196:S Phase / Q000235:genetics / Q000502:physiology; D014161:Transduction, Genetic
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D009841:Oligonucleotides; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; D005982:Glutathione Transferase; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes
Mol Cell. 1998 Jun;1(7):969-79
9651580
Science. 1998 Apr 24;280(5363):590-2
9554850
Science. 1999 Jun 25;284(5423):2174-7
10381882
Nature. 2004 Nov 18;432(7015):406-11
15525939
Biochem J. 2005 Feb 15;386(Pt 1):85-91
15473865
Cell. 1999 Dec 10;99(6):577-87
10612394
J Biol Chem. 2000 May 26;275(21):16030-6
10748127
Mol Cell Biol. 2000 Jul;20(13):4859-69
10848611
J Cell Biol. 2000 Aug 21;150(4):707-18
10952997
Mol Cell. 2001 May;7(5):1111-7
11389857
Cell. 2001 Jul 13;106(1):5-8
11461695
Science. 2001 Aug 3;293(5531):853-7
11387442
Mol Cell. 2001 Nov;8(5):1129-35
11741547
Genes Dev. 2001 Dec 15;15(24):3296-307
11751635
Nat Genet. 2002 Mar;30(3):290-4
11850621
Nature. 2002 Aug 1;418(6897):562-6
12152085
J Cell Biol. 2002 Dec 23;159(6):957-69
12486110
Mol Biol Cell. 2003 Jan;14(1):274-87
12529443
Nature. 2003 Feb 27;421(6926):952-6
12607003
Nature. 2003 Feb 27;421(6926):957-61
12607004
Nature. 2003 Feb 27;421(6926):961-6
12607005
Nat Rev Cancer. 2003 Mar;3(3):155-68
12612651
Genes Dev. 2003 Apr 15;17(8):1019-29
12704081
Mol Cell. 2003 Apr;11(4):1055-66
12718890
EMBO Rep. 2003 Sep;4(9):844-9
12949583
EMBO J. 2003 Oct 15;22(20):5612-21
14532133
EMBO J. 2003 Dec 15;22(24):6610-20
14657032
Mol Cell Proteomics. 2003 Dec;2(12):1319-30
14534352
Science. 2004 Apr 2;304(5667):93-6
15064416
Cell. 1998 May 1;93(3):467-76
9590180
Cell. 1998 May 1;93(3):477-86
9590181
Biochem J. 2004 Apr 15;379(Pt 2):283-9
14705965
Mol Cell. 2003 Dec;12(6):1511-23
14690604
EMBO J. 2004 Jul 7;23(13):2641-50
15175657
Genes Dev. 2004 Aug 15;18(16):2024-35
15314027
Cell. 2004 Sep 3;118(5):545-53
15339660
Cell. 2004 Sep 17;118(6):699-713
15369670
Science. 2004 Oct 8;306(5694):279-83
15345777
Science. 1995 Jun 23;268(5218):1749-53
7792600
Prog Nucleic Acid Res Mol Biol. 1998;61:65-131
9752719