#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability


Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.


Vyšlo v časopise: A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003899
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003899

Souhrn

Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.


Zdroje

1. KunkelTA (2004) DNA replication fidelity. J Biol Chem 279: 16895–16898.

2. IyerRR, PluciennikA, BurdettV, ModrichPL (2006) DNA mismatch repair: functions and mechanisms. Chem Rev 106: 302–323.

3. ChenC, UmezuK, KolodnerRD (1998) Chromosomal rearrangements occur in S. cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair. Mol Cell 2: 9–22.

4. ChenC, KolodnerRD (1999) Gross chromosomal rearrangements in Saccharomyces cerevisiae replication and recombination defective mutants. Nat Genet 23: 81–85.

5. HarfeBD, Jinks-RobertsonS (2000) DNA polymerase zeta introduces multiple mutations when bypassing spontaneous DNA damage in Saccharomyces cerevisiae. Mol Cell 6: 1491–1499.

6. KunkelTA, BebenekK (2000) DNA replication fidelity. Annu Rev Biochem 69: 497–529.

7. DrakeJW (1991) A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci USA 88: 7160–7164.

8. GeacintovNE, SwenbergCE (1991) Chemical, molecular biology, and genetic techniques for correlating DNA base damage induced by ionizing radiation with biological end points. Basic Life Sci 58: 453–473 discussion 473–454.

9. KolodnerRD, PutnamCD, MyungK (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297: 552–557.

10. MalkovaA, HaberJE (2012) Mutations arising during repair of chromosome breaks. Annu Rev Genet 46: 455–473.

11. BoiteuxS, Jinks-RobertsonS (2013) DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae. Genetics 193: 1025–1064.

12. San FilippoJ, SungP, KleinH (2008) Mechanism of eukaryotic homologous recombination. Annu Rev Biochem 77: 229–257.

13. PursellZF, IsozI, LundstromEB, JohanssonE, KunkelTA (2007) Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 317: 127–130.

14. Nick McElhinnySA, GordeninDA, StithCM, BurgersPM, KunkelTA (2008) Division of labor at the eukaryotic replication fork. Mol Cell 30: 137–144.

15. KolodnerRD, MarsischkyGT (1999) Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9: 89–96.

16. HarfeBD, Jinks-RobertsonS (2000) DNA Mismatch Repair and Genetic Instability. Annu Rev Genet 34: 359–399.

17. SurteesJA, ArguesoJL, AlaniE (2004) Mismatch repair proteins: key regulators of genetic recombination. Cytogenet Genome Res 107: 146–159.

18. KunkelTA, ErieDA (2005) DNA Mismatch Repair. Annu Rev Biochem 74: 681–710.

19. ModrichP (2006) Mechanisms in eukaryotic mismatch repair. J Biol Chem 281: 30305–30309.

20. LiGM (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18: 85–98.

21. Pena-DiazJ, JiricnyJ (2012) Mammalian mismatch repair: error-free or error-prone? Trends Biochem Sci 37: 206–214.

22. KadyrovFA, DzantievL, ConstantinN, ModrichP (2006) Endonucleolytic function of MutLalpha in human mismatch repair. Cell 126: 297–308.

23. KadyrovFA, HolmesSF, AranaME, LukianovaOA, O'DonnellM, et al. (2007) Saccharomyces cerevisiae MutLalpha is a mismatch repair endonuclease. J Biol Chem 282: 37181–37190.

24. PluciennikA, DzantievL, IyerRR, ConstantinN, KadyrovFA, et al. (2010) PCNA function in the activation and strand direction of MutLalpha endonuclease in mismatch repair. Proc Natl Acad Sci US A 107: 16066–16071.

25. IyerRR, PluciennikA, GenschelJ, TsaiMS, BeeseLS, et al. (2010) MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta. J Biol Chem 285: 11730–11739.

26. ConstantinN, DzantievL, KadyrovFA, ModrichP (2005) Human mismatch repair: Reconstitution of a nick-directed bidirectional reaction. J Biol Chem 280: 39752–39761.

27. KadyrovFA, GenschelJ, FangY, PenlandE, EdelmannW, et al. (2009) A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair. Proc Natl Acad Sci USA 106: 8495–8500.

28. StrandM, ProllaTA, LiskayRM, PetesTD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365: 274–276.

29. MorrisonA, JohnsonAL, JohnstonLH, SuginoA (1993) Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J 12: 1467–1473.

30. ParsonsR, LiGM, LongleyMJ, FangWH, PapadopoulosN, et al. (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75: 1227–1236.

31. AlbertsonTM, OgawaM, BugniJM, HaysLE, ChenY, et al. (2009) DNA polymerase epsilon and delta proofreading suppress discrete mutator and cancer phenotypes in mice. Proc Natl Acad Sci U S A 106: 17101–17104.

32. GrothA, RochaW, VerreaultA, AlmouzniG (2007) Chromatin challenges during DNA replication and repair. Cell 128: 721–733.

33. RansomM, DenneheyBK, TylerJK (2010) Chaperoning histones during DNA replication and repair. Cell 140: 183–195.

34. XuF, ZhangK, GrunsteinM (2005) Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121: 375–385.

35. MasumotoH, HawkeD, KobayashiR, VerreaultA (2005) A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature 436: 294–298.

36. CelicI, MasumotoH, GriffithWP, MeluhP, CotterRJ, et al. (2006) The sirtuins Hst3 and Hst4p preserve genome integrity by controlling histone h3 lysine 56 deacetylation. Curr Biol 16: 1280–1289.

37. SchneiderJ, BajwaP, JohnsonFC, BhaumikSR, ShilatifardA (2006) Rtt109 is required for proper H3K56 acetylation: a chromatin mark associated with the elongating RNA polymerase II. J Biol Chem 281: 37270–37274.

38. HanJ, ZhouH, HorazdovskyB, ZhangK, XuRM, et al. (2007) Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication. Science 315: 653–655.

39. DriscollR, HudsonA, JacksonSP (2007) Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56. Science 315: 649–652.

40. TsubotaT, BerndsenCE, ErkmannJA, SmithCL, YangL, et al. (2007) Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes. Mol Cell 25: 703–712.

41. ChenCC, CarsonJJ, FeserJ, TamburiniB, ZabaronickS, et al. (2008) Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell 134: 231–243.

42. HylandEM, CosgroveMS, MolinaH, WangD, PandeyA, et al. (2005) Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol Cell Biol 25: 10060–10070.

43. FrancoAA, LamWM, BurgersPM, KaufmanPD (2005) Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C. Genes Dev 19: 1365–1375.

44. YuanJ, PuM, ZhangZ, LouZ (2009) Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8: 1747–1753.

45. TjeertesJV, MillerKM, JacksonSP (2009) Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28: 1878–1889.

46. MaasNL, MillerKM, DeFazioLG, ToczyskiDP (2006) Cell cycle and checkpoint regulation of histone H3 K56 acetylation by Hst3 and Hst4. Mol Cell 23: 109–119.

47. CelicI, VerreaultA, BoekeJD (2008) Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage. Genetics 179: 1769–1784.

48. Munoz-GalvanS, JimenoS, RothsteinR, AguileraA (2013) Histone H3K56 acetylation, Rad52, and non-DNA repair factors control double-strand break repair choice with the sister chromatid. PLoS Genet 9: e1003237.

49. BrachmannCB, ShermanJM, DevineSE, CameronEE, PillusL, et al. (1995) The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev 9: 2888–2902.

50. HachinoheM, HanaokaF, MasumotoH (2011) Hst3 and Hst4 histone deacetylases regulate replicative lifespan by preventing genome instability in Saccharomyces cerevisiae. Genes Cells 16: 467–477.

51. HaigisMC, SinclairDA (2010) Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 5: 253–295.

52. GuillemetteB, DrogarisP, LinHH, ArmstrongH, Hiragami-HamadaK, et al. (2011) H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genet 7: e1001354.

53. MyungK, PennaneachV, KatsES, KolodnerRD (2003) Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability. Proc Natl Acad Sci USA 100: 6640–6645.

54. ChanJE, KolodnerRD (2011) Rapid analysis of Saccharomyces cerevisiae genome rearrangements by multiplex ligation-dependent probe amplification. PLoS Genet 8: e1002539.

55. PutnamCD, Allen-SolteroSR, MartinezSL, ChanJE, HayesTK, et al. (2012) Bioinformatic identification of genes suppressing genome instability. Proc Natl Acad Sci U S A 109: E3251–3259.

56. KadyrovaLY, Rodriges BlankoE, KadyrovFA (2011) CAF-I-dependent control of degradation of the discontinuous strands during mismatch repair. Proc Natl Acad Sci U S A 108: 2753–2758.

57. SchopfB, BregenhornS, QuivyJP, KadyrovFA, AlmouzniG, et al. (2012) Interplay between mismatch repair and chromatin assembly. Proc Natl Acad Sci U S A 109: 1895–1900.

58. LiF, MaoG, TongD, HuangJ, GuL, et al. (2013) The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha. Cell 153: 590–600.

59. ShcherbakovaPV, KunkelTA (1999) Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations. Mol Cell Biol 19: 3177–3183.

60. RechtJ, TsubotaT, TannyJC, DiazRL, BergerJM, et al. (2006) Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis. Proc Natl Acad Sci U S A 103: 6988–6993.

61. ErkmannJA, KaufmanPD (2009) A negatively charged residue in place of histone H3K56 supports chromatin assembly factor association but not genotoxic stress resistance. DNA Repair (Amst) 8: 1371–1379.

62. BittermanKJ, AndersonRM, CohenHY, Latorre-EstevesM, SinclairDA (2002) Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 277: 45099–45107.

63. MichelJJ, McCarvilleJF, XiongY (2003) A role for Saccharomyces cerevisiae Cul8 ubiquitin ligase in proper anaphase progression. J Biol Chem 278: 22828–22837.

64. KroganNJ, CagneyG, YuH, ZhongG, GuoX, et al. (2006) Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440: 637–643.

65. WatanabeS, Radman-LivajaM, RandoOJ, PetersonCL (2013) A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme. Science 340: 195–199.

66. DionMF, KaplanT, KimM, BuratowskiS, FriedmanN, et al. (2007) Dynamics of replication-independent histone turnover in budding yeast. Science 315: 1405–1408.

67. MorrisonA, SuginoA (1994) The 3′-->5′ exonucleases of both DNA polymerases delta and epsilon participate in correcting errors of DNA replication in Saccharomyces cerevisiae. Mol Gen Genet 242: 289–296.

68. TranHT, KeenJD, KrickerM, ResnickMA, GordeninDA (1997) Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants. Mol Cell Biol 17: 2859–2865.

69. TranHT, GordeninDA, ResnickMA (1999) The 3′-->5′ exonucleases of DNA polymerases delta and epsilon and the 5′-->3′ exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. Mol Cell Biol 19: 2000–2007.

70. KirchnerJM, TranH, ResnickMA (2000) A DNA polymerase epsilon mutant that specifically causes +1 frameshift mutations within homonucleotide runs in yeast. Genetics 155: 1623–1632.

71. NorthamMR, RobinsonHA, KochenovaOV, ShcherbakovaPV (2010) Participation of DNA polymerase zeta in replication of undamaged DNA in Saccharomyces cerevisiae. Genetics 184: 27–42.

72. MarsischkyGT, FilosiN, KaneMF, KolodnerR (1996) Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev 10: 407–420.

73. MorrisonA, BellJB, KunkelTA, SuginoA (1991) Eukaryotic DNA polymerase amino acid sequence required for 3′----5′ exonuclease activity. Proc NatlAcad Sci U S A 88: 9473–9477.

74. JinYH, ObertR, BurgersPM, KunkelTA, ResnickMA, et al. (2001) The 3′-->5′ exonuclease of DNA polymerase delta can substitute for the 5′ flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability. Proc Natl Acad Sci U S A 98: 5122–5127.

75. FillinghamJ, RechtJ, SilvaAC, SuterB, EmiliA, et al. (2008) Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109. Mol Cell Biol 28: 4342–4353.

76. BerndsenCE, TsubotaT, LindnerSE, LeeS, HoltonJM, et al. (2008) Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75. Nat Struct Mol Biol 15: 948–956.

77. KimN, HuangSN, WilliamsJS, LiYC, ClarkAB, et al. (2011) Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 332: 1561–1564.

78. MyungK, ChenC, KolodnerRD (2001) Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature 411: 1073–1076.

79. MyungK, DattaA, KolodnerRD (2001) Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell 104: 397–408.

80. MorrisonA, ChristensenRB, AlleyJ, BeckAK, BernstineEG, et al. (1989) REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. J Bacteriol 171: 5659–5667.

81. HolbeckSL, StrathernJN (1997) A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147: 1017–1024.

82. CollinsSR, MillerKM, MaasNL, RoguevA, FillinghamJ, et al. (2007) Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 446: 806–810.

83. LukeB, VersiniG, JaquenoudM, ZaidiIW, KurzT, et al. (2006) The cullin Rtt101p promotes replication fork progression through damaged DNA and natural pause sites. Curr Biol 16: 786–792.

84. HannaJS, KrollES, LundbladV, SpencerFA (2001) Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol Cell Biol 21: 3144–3158.

85. BylundGO, BurgersPM (2005) Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex. Mol Cell Biol 25: 5445–5455.

86. RocheH, GietzRD, KunzBA (1995) Specificities of the Saccharomyces cerevisiae rad6, rad18, and rad52 mutators exhibit different degrees of dependence on the REV3 gene product, a putative nonessential DNA polymerase. Genetics 140: 443–456.

87. ShahbazianMD, GrunsteinM (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76: 75–100.

88. JinYH, ClarkAB, SlebosRJ, Al-RefaiH, TaylorJA, et al. (2003) Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet 34: 326–329.

89. PutnamCD, HayesTK, KolodnerRD (2009) Specific pathways prevent duplication-mediated genome rearrangements. Nature 460: 984–989.

90. LobachevKS, GordeninDA, ResnickMA (2002) The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Cell 108: 183–193.

91. SaparbaevM, PrakashL, PrakashS (1996) Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics 142: 727–736.

92. SugawaraN, PaquesF, ColaiacovoM, HaberJE (1997) Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Proc Natl Acad Sci U S A 94: 9214–9219.

93. StudamireB, PriceG, SugawaraN, HaberJE, AlaniE (1999) Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Mol Cell Biol 19: 7558–7567.

94. LyndakerAM, AlaniE (2009) A tale of tails: insights into the coordination of 3′ end processing during homologous recombination. Bioessays 31: 315–321.

95. HaberJE (1995) In vivo biochemistry: physical monitoring of recombination induced by site-specific endonucleases. Bioessays 17: 609–620.

96. McGrawBR, MarinusMG (1980) Isolation and characterization of dam+ revertants and suppressor mutations that modify secondary phenotypes of dam-3 strains of Escherichia coli K-12. Mol Gen Genet 178: 309–315.

97. YunM, WuJ, WorkmanJL, LiB (2011) Readers of histone modifications. Cell Res 21: 564–578.

98. UmarA, BuermeyerAB, SimonJA, ThomasDC, ClarkAB, et al. (1996) Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell 87: 65–73.

99. DzantievL, ConstantinN, GenschelJ, IyerRR, BurgersPM, et al. (2004) A defined human system that supports bidirectional mismatch-provoked excision. Mol Cell 15: 31–41.

100. SuttonA, BucariaJ, OsleyMA, SternglanzR (2001) Yeast ASF1 protein is required for cell cycle regulation of histone gene transcription. Genetics 158: 587–596.

101. GueldenerU, HeinischJ, KoehlerGJ, VossD, HegemannJH (2002) A second set of loxP marker cassettes for Cre-mediated multiple gene knockouts in budding yeast. Nucleic Acids Res 30: e23.

102. GietzRD, WoodsRA (2002) Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350: 87–96.

103. MaWT, GV SandriGV, SarkarS (1992) Analysis of the Luria-Delbrück distribution using discrete convolution powers. J Appl Prob 29: 255–267.

104. AsterisG, SarkarS (1996) Bayesian procedures for the estimation of mutation rates from fluctuation experiments. Genetics 142: 313–326.

105. HallBM, MaCX, LiangP, SinghKK (2009) Fluctuation analysis CalculatOR: a web tool for the determination of mutation rate using Luria-Delbruck fluctuation analysis. Bioinformatics 25: 1564–1565.

106. RoscheWA, FosterPL (2000) Determining mutation rates in bacterial populations. Methods 20: 4–17.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#