The Uve1 Endonuclease Is Regulated by the White Collar Complex to Protect from UV Damage

English version České info

The pathogenic fungus Cryptococcus neoformans uses the Bwc1-Bwc2 photoreceptor complex to regulate mating in response to light, virulence and ultraviolet radiation tolerance. How the complex controls these functions is unclear. Here, we identify and characterize a gene in Cryptococcus, UVE1, whose mutation leads to a UV hypersensitive phenotype. The homologous gene in fission yeast Schizosaccharomyces pombe encodes an apurinic/apyrimidinic endonuclease acting in the UVDE-dependent excision repair (UVER) pathway. C. neoformans UVE1 complements a S. pombe uvde knockout strain. UVE1 is photoregulated in a Bwc1-dependent manner in Cryptococcus, and in Neurospora crassa and Phycomyces blakesleeanus that are species that represent two other major lineages in the fungi. Overexpression of UVE1 in bwc1 mutants rescues their UV sensitivity phenotype and gel mobility shift experiments show binding of Bwc2 to the UVE1 promoter, indicating that UVE1 is a direct downstream target for the Bwc1-Bwc2 complex. Uve1-GFP fusions localize to the mitochondria. Repair of UV-induced damage to the mitochondria is delayed in the uve1 mutant strain. Thus, in C. neoformans UVE1 is a key gene regulated in response to light that is responsible for tolerance to UV stress for protection of the mitochondrial genome.

Vyšlo v časopise: The Uve1 Endonuclease Is Regulated by the White Collar Complex to Protect from UV Damage. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003769
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003769

Souhrn

Zdroje

1. Rodriguez-RomeroJ, HedtkeM, KastnerC, MüllerS, FischerR (2010) Fungi, hidden in soil or up in the air: light makes a difference. Annu Rev Microbiol 64 : 585–610.

2. IdnurmA, VermaS, CorrochanoLM (2010) A glimpse into the basis of vision in the kingdom Mycota. Fungal Genet Biol 47 : 881–892.

3. TischD, SchomollM (2010) Light regulation of metabolic pathways in fungi. Appl Microbiol Biotechnol 85 : 1259–1277.

4. BallarioP, VittoriosoP, MagrelliA, TaloraC, CabibboA, et al. (1996) White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. EMBO J 15 : 1650–1657.

5. TaloraC, FranchiL, LindenH, BallarioP, MacinoG (1999) Role of a white collar-1-white collar-2 complex in blue-light signal transduction. EMBO J 18 : 4961–4968.

6. LiuY, HeQ, ChengP (2003) Photoreception in Neurospora: a tale of two White Collar proteins. Cell Mol Life Sci 60 : 2131–2138.

7. ChenCH, DunlapJC, LorosJJ (2010) Neurospora illuminates fungal photoreception. Fungal Genet Biol 47 : 922–929.

8. CrosthwaiteSK, DunlapJC, LorosJJ (1997) Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. Science 276 : 763–769.

9. DunlapJC, LorosJJ (2004) The Neurospora circadian system. J Biol Rhythms 19 : 414–424.

10. LiuY, Bell-PedersenD (2006) Circadian rhythms in Neurospora crassa and other filamentous fungi. Eukaryot Cell 5 : 1184–1193.

11. ChenCH, RingelbergCS, GrossRH, DunlapJC, LorosJJ (2009) Genome-wide analysis of light-inducible responses reveals hierarchical light signalling in Neurospora. EMBO J 28 : 1029–1042.

12. OlmedoM, Ruger-HerrerosC, CorrochanoLM (2010) Regulation by blue light of the fluffy gene encoding a major regulator of conidiation in Neurospora crassa. Genetics 184 : 651–658.

13. HeQ, ChengP, YangY, WangL, GardnerKH, et al. (2002) White collar-1, a DNA binding transcription factor and a light sensor. Science 297 : 840–843.

14. FroehlichAC, LiuY, LorosJJ, DunlapJC (2002) White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter. Science 297 : 815–819.

15. LengelerKB, WangP, CoxGM, PerfectJR, HeitmanJ (2000) Identification of the MATa mating-type locus of Cryptococcus neoformans reveals a serotype A MATa strain thought to have been extinct. Proc Natl Acad Sci U S A 97 : 14455–14460.

16. Heitman J, Kozel TR, Kwon-Chung KJ, Perfect JR, Casadevall A (2011) Cryptococcus From Human Pathogen To Model Yeast. Washington, DC: ASM Press.

17. IdnurmA, HeitmanJ (2005) Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol 3: e95.

18. LuYK, SunKH, ShenWC (2005) Blue light negatively regulates the sexual filamentation via the Cwc1 and Cwc2 proteins in Cryptococcus neoformans. Mol Microbiol 56 : 480–491.

19. IdnurmA, HeitmanJ (2010) Ferrochelatase is a conserved downstream target of the blue light-sensing White collar complex in fungi. Microbiology 156 : 2393–2407.

20. JungWH, ShamA, LianT, SinghA, KosmanDJ, et al. (2008) Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog 4: e45.

21. PregueiroAM, LiuQ, BakerCL, DunlapJC, LorosJJ (2006) The Neurospora checkpoint kinase 2: a regulatory link between the circadian and cell cycles. Science 313 : 644–649.

22. GamsbyJJ, LorosJJ, DunlapJC (2009) A phylogenetically conserved DNA damage response resets the circadian clock. J Biol Rhythms 24 : 193–202.

23. WakabayashiM, IshiiC, InoueH, TanakaS (2008) Genetic analysis of CHK1 and CHK2 homologues revealed a unique cross talk between ATM and ATR pathways in Neurospora crassa. DNA Repair 7 : 1951–1961.

24. IdnurmA, WaltonFJ, FloydA, ReedyJL, HeitmanJ (2009) Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis. Eukaryot Cell 8 : 315–326.

25. TakaoM, YonemasuR, YamamotoK, YasuiA (1996) Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog. Nucleic Acids Res 24 : 1267–1271.

26. KannoS, IwaiS, TakaoM, YasuiA (1999) Repair of apurinic/apyrimidinic sites by UV damage endonuclease; a repair protein for UV and oxidative damage. Nucleic Acids Res 27 : 3096–3103.

27. YajimaH, TakaoM, YasuhiraS, ZhaoJH, IshiiC, et al. (1995) A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. EMBO J 14 : 2393–2399.

28. KaurB, FraserJLA, FreyerGA, DaveyS, DoetschPW (1999) A Uve1p-mediated mismatch repair pathway in Schizosaccharomyces pombe. Mol Cell Biol 19 : 4703–4710.

29. PaspalevaK, MoolenaarGF, GoosenN (2009) Damage recognition by UV damage endonuclease from Schizosaccharomyces pombe. DNA Repair 8 : 600–611.

30. KaurB, DoetschPW (2000) Ultraviolet damage endonuclease (Uve1p): a structure and strand-specific DNA endonuclease. Biochemistry 39 : 5788–5796.

31. FraserJLA, NeillE, DaveyS (2003) Fission yeast Uve1 and Apn2 function in distinct oxidative damage repair pathways in vivo. DNA Repair 2 : 1253–1267.

32. YasuhiraS, YasuiA (2000) Alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe operates both in nucleus and in mitochondria. J Biol Chem 275 : 11824–11828.

33. EarlAM, RankinSK, KimKP, LamendolaON, BattistaJR (2002) Genetic evidence that the uvsE gene product of Deinococcus radiodurans R1 is a UV damage endonuclease. J Bacteriol 184 : 1003–1009.

34. GoosenN, MoolenaarGF (2008) Repair of UV damage in bacteria. DNA Repair 7 : 353–379.

35. MeulenbroekEM, PaspalevaK, ThomassenEAJ, AbrahamsJP, GoosenN, et al. (2009) Involvement of a carboxylated lysine in UV damage endonuclease. Protein Sci 18 : 549–558.

36. MeulenbroekEM, Peron CaneC, JalaI, IwaiS, MoolenaarGF, et al. (2013) UV damage endonuclease employs a novel dual-dinucleotide flipping mechanism to recognize different DNA lesions. Nucleic Acids Res 41 : 1363–1371.

37. PaspalevaK, ThomassenE, PannuNS, IwaiS, MoolenaarGF, et al. (2007) Crystal structure of the DNA repair enzyme ultraviolet damage endonuclease. Structure 15 : 1316–1324.

38. LiuOW, ChunCD, ChowED, ChenC, MadhaniHD, et al. (2008) Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135 : 174–188.

39. SanzC, Rodríguez-RomeroJ, IdnurmA, ChristieJM, HeitmanJ, et al. (2009) Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism. Proc Natl Acad Sci U S A 106 : 7095–7100.

40. YonemasuR, McCreadySJ, MurrayJM, OsmanF, TakaoM, et al. (1997) Characterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe. Nucleic Acids Res 25 : 1553–1558.

41. BowmanKK, SidikK, SmithCA, TaylorJS, DoetschPW, et al. (1994) A new ATP-independent DNA endonuclease from Schizosaccharomyces pombe that recognizes cyclobutane pyrimidine dimers and 6-4 photoproducts. Nucleic Acids Res 22 : 3026–3032.

42. HunterSE, JungD, Di GiulioRT, MeyerJN (2010) The QPCR assay for analysis of mitochondrial DNA damage, repair, and relative copy number. Methods 51 : 444–451.

43. LiuZ, ButowRA (2006) Mitochondrial retrograde signaling. Annu Rev Genet 40 : 159–185.

44. Al-MehdiAB, PastukhVM, SwigerBM, ReedDJ, PatelMR, et al. (2012) Perinuclear mitochondrial clustering creates an oxidant-rich nuclear domain required for hypoxia-induced transcription. Sci Signal 5: ra47.

45. UraK, ArakiM, SaekiH, MasutaniC, ItoT, et al. (2001) ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes. EMBO J 20 : 2004–2014.

46. GilkersonR, BravoL, GarciaI, GaytanN, HerreraA, et al. (2013) The mitochondrial nucleoid: integrating mitochondrial DNA into cellular homeostasis. Cold Spring Harb Perspect Biol 5: a011080.

47. ZhangL, JonesK, GongF (2009) The molecular basis of chromatin dynamics during nucleotide excision repair. Biochem Cell Biol 87 : 265–272.

48. Owusu-AnsahE, YavariA, MandalS, BanerjeeU (2008) Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat Genet 40 : 356–361.

49. LambTM, GoldsmithCS, BennettL, FinchKE, Bell-PedersenD (2011) Direct transcriptional control of a p38 MAPK pathway by the circadian clock in Neurospora crassa. PLoS One 6: e27149.

50. KangTH, ReardonJT, KempM, SancarA (2009) Circadian oscillation of nucleotide excision repair in mammalian brain. Proc Natl Acad Sci U S A 106 : 2864–2867.

51. KangTH, Lindsey-BoltzLA, ReardonJT, SancarA (2010) Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A 107 : 4890–4895.

52. Rosales-SaavedraT, Esquivel-NaranjoEU, Casas-FloresS, Martínez-HernándezP, Ibarra-LacletteE, et al. (2006) Novel light-regulated genes in Trichoderma atroviride: a dissection by cDNA microarrays. Microbiology 152 : 3305–3317.

53. Ruger-HerrerosC, Rodríguez-RomeroJ, Fernández-BarrancoR, OlmedoM, FischerR, et al. (2011) Regulation of conidiation by light in Aspergillus nidulans. Genetics 188 : 809–822.

54. SwartzlanderDB, GriffithsLM, LeeJ, DegtyarevaNP, DoetschPW, et al. (2010) Regulation of base excision repair: Ntg1 nuclear and mitochondrial dynamic localization in response to genotoxic stress. Nucleic Acids Res 38 : 3963–3974.

55. CouthouisJ, HartMP, ShorterJ, DeJesus-HernandezM, ErionR, et al. (2011) A yeast functional screen predicts new candidate ALS disease genes. Proc Natl Acad Sci U S A 108 : 20881–20890.

56. HungMC, LinkW (2011) Protein localization in disease and therapy. J Cell Sci 124 : 3381–3392.

57. SalichosL, RokasA (2010) The diversity and evolution of circadian clock proteins in fungi. Mycologia 102 : 269–278.

58. LosiA, PolveriniE, QuestB, GärtnerW (2002) First evidence for phototropin-related blue-light receptors in prokaryotes. Biophys J 82 : 2627–2634.

59. YasuiA, YajimaH, KobayashiT, EkerAP, OikawaA (1992) Mitochondrial DNA repair by photolyase. Mutat Res 273 : 231–236.

60. GreenG, MacQuillanAM (1980) Photorepair of ultraviolet-induced petite mutational damage in Saccharomyces cerevisiae requires the product of the PHR1 gene. J Bacteriol 144 : 826–829.

61. ToffalettiDL, RudeTH, JohnstonSA, DurackDT, PerfectJR (1993) Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol 175 : 1405–1411.

62. PitkinJW, PanaccioneDG, WaltonJD (1996) A putative cyclic peptide efflux pump encoded by the TOXA gene of the plant-pathogenic fungus Cochliobolus carbonum. Microbiology 142 : 1557–1565.

63. MylonakisE, MorenoR, El KhouryJB, IdnurmA, HeitmanJ, et al. (2005) Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect Immun 73 : 3842–3850.

64. Kwon-ChungKJ, EdmanJC, WickesBL (1992) Genetic association of mating types and virulence in Cryptococcus neoformans. Infect Immun 60 : 602–605.

65. HoldenNS, TaconCE (2011) Principles and problems of the electrophoretic mobility shift assay. J Pharmacol Toxicol Methods 63 : 7–14.