Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

Journal of Clinical Investigation

Volumn 125, Issue 1, 2015, Pages 413-424

  Günther, Claudia ^a   Kind, Barbara ^a   Reijns, Martin A M ^b   Berndt, Nicole ^a   Martinez Bueno, Manuel ^c   Wolf, Christine ^a   Tüngler, Victoria ^a   Chara, Osvaldo ^d,e   Lee, Young Ae ^f   Hübner, Norbert ^f   Bicknell, Louise ^b   Blum, Sophia ^a   Krug, Claudia ^a   Schmidt, Franziska ^a   Kretschmer, Stefanie ^a   Koss, Sarah ^a   Astell, Katy R ^b   Ramantani, Georgia ^g   Bauerfeind, Anja ^f   Morris, David L ^h   Graham, Deborah S Cunninghame ^h   Bubeck, Doryen ⁱ   Leitch, Andrea ^b   Ralston, Stuart H ^j   Blackburn, Elizabeth A ^j   Gahr, Manfred ^a   Witte, Torsten ^k   Vyse, Timothy J ^h   Melchers, Inga ^l   Mangold, Elisabeth ^m,n   Nöthen, Markus M ^m,n,o   Aringer, Martin ^a   Kuhn, Annegret ^p   Lüthke, Kirsten ^q   Unger, Leonore ^r   Bley, Annette ^s   Lorenzi, Alice ^t   Isaacs, John D ^t   Alexopoulou, Dimitra ^u   Conrad, Karsten ^a   Dahl, Andreas ^u   Roers, Axel ^a   Alarcon Riquelme, Marta E ^c,v   Jackson, Andrew P ^b   Lee Kirsch, Min Ae ^a   more..

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c UNIVERSITY OF GRANADA   (Spain)

^d DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^e UNIVERSIDAD NACIONAL DE LA PLATA   (Argentina)

^f MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^g UNIVERSITY OF FREIBURG   (Germany)

^h KING'S COLLEGE LONDON   (United Kingdom)

ⁱ IMPERIAL COLLEGE LONDON   (United Kingdom)

^j UNIVERSITY OF EDINBURGH   (United Kingdom)

^k HANNOVER MEDICAL SCHOOL   (Germany)

^l UNIVERSITY OF FREIBURG   (Germany)

^m UNIVERSITY HOSPITAL BONN   (Germany)

ⁿ GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^o UNIVERSITY OF BONN   (Germany)

^p UNIVERSITY OF MÜNSTER   (Germany)

^q Schwerpunktpraxis Rheumatologie   (Germany)

^r ACADEMIC TEACHING HOSPITAL DRESDEN FRIEDRICHSTADT   (Germany)

^s UNIVERSITY OF HAMBURG   (Germany)

^t NEWCASTLE UNIVERSITY   (United Kingdom)

^u CENTER FOR REGENERATIVE THERAPIES DRESDEN   (Germany)

^v OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; GENOMIC DNA; INTERFERON; OLIGONUCLEOTIDE; PROTEIN P53; PYRIMIDINE DIMER; RIBONUCLEASE H2; RIBONUCLEOTIDE; SYNTHETIC DNA; UNCLASSIFIED DRUG; RIBONUCLEASE H; RIBONUCLEASE HII;

ADULT; AICARDI GOUTIERES SYNDROME; ANIMAL CELL; ARTICLE; AUTOIMMUNITY; CELL CYCLE PROGRESSION; CELL NUCLEUS; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CHILD; COMPARATIVE STUDY; CONTROLLED STUDY; COVALENT BOND; DIMERIZATION; DISEASE PREDISPOSITION; DNA CONFORMATION; DNA DAMAGE; DNA ISOLATION; DNA STRUCTURE; ENZYME ACTIVITY; ENZYME STABILITY; EXCISION REPAIR; FEMALE; FIBROBLAST; GENE FREQUENCY; GENE FUNCTION; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC VARIABILITY; HETEROZYGOSITY; HUMAN; HUMAN CELL; INNATE IMMUNITY; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; SENESCENCE; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; ULTRAVIOLET IRRADIATION; UPREGULATION; CELL CULTURE; DNA REPAIR; GENE EXPRESSION; GENETICS; HETEROZYGOTE; METABOLISM;

AUTOIMMUNITY; CELL PROLIFERATION; CELLS, CULTURED; DNA MUTATIONAL ANALYSIS; DNA REPAIR; GENE EXPRESSION; HETEROZYGOTE; HUMANS; INTERFERON TYPE I; LUPUS ERYTHEMATOSUS, SYSTEMIC; PYRIMIDINE DIMERS; RIBONUCLEASE H;

EID: 84920413492     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI78001     Document Type: Article

References (63)

1. Atianand MK, Fitzgerald KA. Molecular basis of DNA recognition in the immune system. J Immunol. 2013;190(5):1911-1918.
2. Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol. 2006;6(11):823-835.
3. Ronnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin Rheumatol. 2009;21(5):471-477.
4. Leadbetter EA, Rifkin IR, Hohlbaum AM, Beau-dette BC, Shlomchik MJ, Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature. 2002;416(6881):603-607.
5. Lovgren T, Eloranta ML, Bave U, Alm GV, Ronn-blom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004;50(6):1861-1872.
6. James JA, Harley JB, Scofield RH. Role of viruses in systemic lupus erythematosus and Sjogren syndrome. Curr Opin Rheumatol. 2001;13(5):370-376.
7. Bijl M, Kallenberg CG. Ultraviolet light and cutaneous lupus. Lupus. 2006;15(11):724-727.
8. Aicardi J, Goutieres F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol. 1984;15(1):49-54.
9. Lebon P, Badoual J, Ponsot G, Goutieres F, Hemeury-Cukier F, Aicardi J. Intrathecal synthesis of interferon-α in infants with progressive familial encephalopathy. J Neurol Sci. 1988;84(2-3):201-208.
10. Ramantani G, et al. Expanding the pheno-typic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome. Ar thritis Rheum. 2010;62(5):1469-1477.
11. Rice GI, et al. Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNA-SEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013;12(12):1159-1169.
12. Crow YJ, et al. Mutations in genes encoding ribo-nuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat Genet. 2006;38(8):910-916.
13. Crow YJ, et al. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat Genet. 2006;38(8):917-920.
14. Rice G, et al. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am J Hum Genet. 2007;80(4):811-815.
15. Lee-Kirsch MA, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med. 2007;85(5):531-537.
16. Lee-Kirsch MA, et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39(9):1065-1067.
17. Rice GI, et al. Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet. 2009;41(7):829-832.
18. Ravenscroft JC, Suri M, Rice GI, Szynkiewicz M, Crow YJ. Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. Am J Med Genet A. 2011;155A(1):235-237.
19. Rice GI, et al. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nat Genet. 2012;44(11):1243-1248.
20. Rice GI, et al. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phe-notypes associated with upregulated type I interferon signaling. Nat Genet. 2014;46(5):503-509.
21. Lee-Kirsch MA, Wolf C, Gunther C. Aicardi-Goutieres syndrome: a model disease for systemic autoimmunity. Clin Exp Immunol. 2014;175(1):17-24.
22. Nick McElhinny SA, et al. Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol. 2010;6(10):774-781.
23. Reijns MA, et al. Enzymatic removal of ribo-nucleotides from DNA is essential for mammalian genome integrity and development. Cell. 2012;149(5):1008-1022.
24. Hiller B, Achleitner M, Glage S, Naumann R, Behrendt R, Roers A. Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity. J Exp Med. 2012;209(8):1419-1426.
25. Chon H, et al. RNase H2 roles in genome integrity revealed by unlinking its activities. Nucleic Acids Res. 2013;41(5):3130-3143.
26. Sparks JL, et al. RNase H2-initiated ribonucleotide excision repair. Mol Cell. 2012;47(6):980-986.
27. Schmidt JL, et al. Family history of autoimmune disease in patients with Aicardi-Goutieres syn-drome. Clin Dev Immunol. 2012;2012:206730.
28. Chon H, et al. Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Res. 2009;37(1):96-110.
29. Reijns MA, et al. The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease. J Biol Chem. 2011;286(12):10530-10539.
30. Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39(7):906-913.
31. Delaneau O, Marchini J, Zagury JF. A linear complexity phasing method for thousands of genomes. Nat Methods. 2012;9(2):179-181.
32. Brzostek-Racine S, Gordon C, Van SS, Reich NC. The DNA damage response induces IFN. J Immunol. 2011;187(10):5336-5345.
33. Yang YG, Lindahl T, Barnes DE. Trex1 exonucle-ase degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. Cell. 2007;131(5):873-886.
34. Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Moroy T. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet. 2000;25(2):177-181.
35. Yasutomo K, et al. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet. 2001;28(4):313-314.
36. Nagata S. Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors. Immunol Rev. 2007;220:237-250.
37. Novarina D, Amara F, Lazzaro F, Plevani P, Muzi-Falconi M. Mind the gap: keeping UV lesions in check. DNA Repair (Amst). 2011;10(7):751-759.
38. Schreier WJ, et al. Thymine dimerization in DNA is an ultrafast photoreaction. Science. 2007;315(5812):625-629.
39. Law YK, Azadi J, Crespo-Hernandez CE, Olmon E, Kohler B. Predicting thymine dimerization yields from molecular dynamics simulations. Biophys J. 2008;94(9):3590-3600.
40. Drew HR, et al. Structure of a B-DNA dodecam-er: conformation and dynamics. Proc Natl Acad Sci U S A. 1981;78(4):2179-2183.
41. Middleton CT, de La HK, Su C, Law YK, Crespo-Hernandez CE, Kohler B. DNA excited-state dynamics: from single bases to the double helix. Annu Re v Phys Chem. 2009;60:217-239.
42. Kundu LM, Linne U, Marahiel M, Carell T. RNA is more UV resistant than DNA: the formation of UV-induced DNA lesions is strongly sequence and conformation dependent. Chemistry. 2004;10(22):5697-5705.
43. DeRose EF, Perera L, Murray MS, Kunkel TA, London RE. Solution structure of the Dickerson DNA dodecamer containing a single ribonucleo-tide. Biochemistry. 2012;51(12):2407-2416.
44. Wu Z, Delaglio F, Tjandra N, Zhurkin VB, Bax A. Overall structure and sugar dynamics of a DNA dodecamer from homo-and heteronuclear dipolar couplings and 31P chemical shift anisotropy. J Biomol NMR. 2003;26(4):297-315.
45. Arbuckle MR, et al. Development of auto-antibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
46. Stetson DB, Ko JS, Heidmann T, Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoim-munity. Cell. 2008;134(4):587-598.
47. Ablasser A, Hemmerling I, Schmid-Burgk JL, Behrendt R, Roers A, Hornung V. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol. 2014;192(12):5993-5997.
48. Yan N, Regalado-Magdos AD, Stiggelbout B, LeeKirsch MA, Lieberman J. The cytosolic exonucle-ase TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat Immunol. 2010;11(11):1005-1013.
49. Munoz-Fontela C, et al. Transcriptional role of p53 in interferon-mediated antiviral immunity. J Exp Med. 2008;205(8):1929-1938.
50. Taniguchi T, Takaoka A. A weak signal for strong responses: interferon-alpha/beta revisited. Nat Rev Mol Cell Biol. 2001;2(5):378-386.
51. Honda K, Yanai H, Takaoka A, Taniguchi T. Regulation of the type I IFN induction: a current view. Int Immunol. 2005;17(11):1367-1378.
52. Hasan M, et al. Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes. Nat Immunol. 2013;14(1):61-71.
53. Honda K, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005;434(7034):772-777.
54. Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994;179(4):1317-1330.
55. Petri M, et al. Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum. 2013;65(4):1011-1021.
56. Liu Y, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507-518.
57. Rigby RE, et al. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J. 2014;33(6):542-558.
58. Al-Mayouf SM, et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43(12):1186-1188.
59. Aitman TJ, et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature. 2006;439(7078):851-855.
60. Tan EM, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271-1277.
61. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
62. Price AL, et al. Pooled association tests for rare variants in exon-resequencing studies. Am J Hum Genet. 2010;86(6):832-838.
63. Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects. J Biol Chem. 2011;286(12):10540-10550.