A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan

English version České info

Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics.

Vyšlo v časopise: A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003329
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003329

Souhrn

Zdroje

1. KaeberleinM (2010) Lessons on longevity from budding yeast. Nature 464: 513–519.

2. MortimerRK, JohnstonJR (1959) Life span of individual yeast cells. Nature 183: 1751–1752.

3. SteinkrausKA, KaeberleinM, KennedyBK (2008) Replicative aging in yeast: the means to the end. Annu Rev Cell Dev Biol 24: 29–54.

4. KennedyBK, GottaM, SinclairDA, MillsK, McNabbDS, et al. (1997) Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell 89: 381–391.

5. DefossezPA, PrustyR, KaeberleinM, LinSJ, FerrignoP, et al. (1999) Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Mol Cell 3: 447–455.

6. WarnerJR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24: 437–440.

7. FrenchSL, OsheimYN, CiociF, NomuraM, BeyerAL (2003) In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes. Mol Cell Biol 23: 1558–1568.

8. KobayashiT, GanleyAR (2005) Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science 309: 1581–1584.

9. GottliebS, EspositoRE (1989) A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56: 771–776.

10. SinclairDA, GuarenteL (1997) Extrachromosomal rDNA circles–a cause of aging in yeast. Cell 91: 1033–1042.

11. KaeberleinM, McVeyM, GuarenteL (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes & Development 13: 2570–2580.

12. BrewerBJ, FangmanWL (1988) A replication fork barrier at the 3′ end of yeast ribosomal RNA genes. Cell 55: 637–643.

13. KobayashiT (2003) The replication fork barrier site forms a unique structure with Fob1p and inhibits the replication fork. Mol Cell Biol 23: 9178–9188.

14. FontanaL, PartridgeL, LongoVD (2010) Extending healthy life span–from yeast to humans. Science 328: 321–326.

15. McCayCM, CrowellMF, MaynardLA (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5: 155–171 discussion 172.

16. TuckerMJ (1979) The effect of long-term food restriction on tumours in rodents. Int J Cancer 23: 803–807.

17. SegallP (1977) Long-term tryptophan restriction and aging in the rat. Aktuelle Gerontol 7: 535–538.

18. MasoroEJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126: 913–922.

19. KennedyBK, SteffenKK, KaeberleinM (2007) Ruminations on dietary restriction and aging. Cell Mol Life Sci 64: 1323–1328.

20. KaeberleinM, KirklandKT, FieldsS, KennedyBK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2: e296 doi:10.1371/journal.pbio.0020296..

21. TsuchiyaM, DangN, KerrEO, HuD, SteffenKK, et al. (2006) Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging Cell 5: 505–514.

22. YvertG, BremRB, WhittleJ, AkeyJM, FossE, et al. (2003) Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet 35: 57–64.

23. PetesTD, BotsteinD (1977) Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast. Proc Natl Acad Sci U S A 74: 5091–5095.

24. FalconAA, ArisJP (2003) Plasmid accumulation reduces life span in Saccharomyces cerevisiae. J Biol Chem 278: 41607–41617.

25. RudraD, WarnerJR (2004) What better measure than ribosome synthesis? Genes Dev 18: 2431–2436.

26. IdeS, MiyazakiT, MakiH, KobayashiT (2010) Abundance of ribosomal RNA gene copies maintains genome integrity. Science 327: 693–696.

27. MillerCA, KowalskiD (1993) cis-acting components in the replication origin from ribosomal DNA of Saccharomyces cerevisiae. Mol Cell Biol 13: 5360–5369.

28. KobayashiT, HoriuchiT, TongaonkarP, VuL, NomuraM (2004) SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. Cell 117: 441–453.

29. Louis E Saccharomyces Genome Resequencing Project. http://www.sanger.ac.uk/research/projects/genomeinformatics/sgrp.html.

30. LitiG, CarterDM, MosesAM, WarringerJ, PartsL, et al. (2009) Population genomics of domestic and wild yeasts. Nature 458: 337–341.

31. GanleyAR, IdeS, SakaK, KobayashiT (2009) The effect of replication initiation on gene amplification in the rDNA and its relationship to aging. Mol Cell 35: 683–693.

32. BoutonAH, SmithMM (1986) Fine-structure analysis of the DNA sequence requirements for autonomous replication of Saccharomyces cerevisiae plasmids. Mol Cell Biol 6: 2354–2363.

33. EatonML, GalaniK, KangS, BellSP, MacAlpineDM (2010) Conserved nucleosome positioning defines replication origins. Genes Dev 24: 748–753.

34. IdeS, WatanabeK, WatanabeH, ShirahigeK, KobayashiT, et al. (2007) Abnormality in initiation program of DNA replication is monitored by the highly repetitive rRNA gene array on chromosome XII in budding yeast. Mol Cell Biol 27: 568–578.

35. KobayashiT, NomuraM, HoriuchiT (2001) Identification of DNA cis elements essential for expansion of ribosomal DNA repeats in Saccharomyces cerevisiae. Mol Cell Biol 21: 136–147.

36. Di RienziSC, LindstromKC, LancasterR, RolczynskiL, RaghuramanMK, et al. (2011) Genetic, genomic, and molecular tools for studying the protoploid yeast, L. waltii. Yeast

37. FriedmanKL, DillerJD, FergusonBM, NylandSV, BrewerBJ, et al. (1996) Multiple determinants controlling activation of yeast replication origins late in S phase. Genes Dev 10: 1595–1607.

38. FriedmanKL, BrewerBJ, FangmanWL (1997) Replication profile of Saccharomyces cerevisiae chromosome VI. Genes Cells 2: 667–678.

39. ShirahigeK, IwasakiT, RashidMB, OgasawaraN, YoshikawaH (1993) Location and characterization of autonomously replicating sequences from chromosome VI of Saccharomyces cerevisiae. Mol Cell Biol 13: 5043–5056.

40. FossM, McNallyFJ, LaurensonP, RineJ (1993) Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae. Science 262: 1838–1844.

41. SuterB, TongA, ChangM, YuL, BrownGW, et al. (2004) The origin recognition complex links replication, sister chromatid cohesion and transcriptional silencing in Saccharomyces cerevisiae. Genetics 167: 579–591.

42. KapahiP, ChenD, RogersAN, KatewaSD, LiPW, et al. (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11: 453–465.

43. DammannR, LucchiniR, KollerT, SogoJM (1993) Chromatin structures and transcription of rDNA in yeast Saccharomyces cerevisiae. Nucleic Acids Res 21: 2331–2338.

44. SteffenKK, MacKayVL, KerrEO, TsuchiyaM, HuD, et al. (2008) Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133: 292–302.

45. StumpferlSW, BrandSE, JiangJC, KoronaB, TiwariA, et al. (2012) Natural genetic variation in yeast longevity. Genome Res

46. KobayashiT (2011) How does genome instability affect lifespan?: roles of rDNA and telomeres. Genes Cells 16: 617–624.

47. RhindN (2006) DNA replication timing: random thoughts about origin firing. Nat Cell Biol 8: 1313–1316.

48. PaquesF, LeungWY, HaberJE (1998) Expansions and contractions in a tandem repeat induced by double-strand break repair. Mol Cell Biol 18: 2045–2054.

49. MayerC, GrummtI (2006) Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25: 6384–6391.

50. ZhangL, MaH, PughBF (2011) Stable and dynamic nucleosome states during a meiotic developmental process. Genome Res 21: 875–884.

51. Sequeira-MendesJ, Diaz-UriarteR, ApedaileA, HuntleyD, BrockdorffN, et al. (2009) Transcription initiation activity sets replication origin efficiency in mammalian cells. PLoS Genet 5: e1000446 doi:10.1371/journal.pgen.1000446..

52. DimitrovaDS (2011) DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci. J Cell Sci 124: 2743–2752.

53. ParedesS, BrancoAT, HartlDL, MaggertKA, LemosB (2011) Ribosomal DNA deletions modulate genome-wide gene expression: “rDNA-sensitive” genes and natural variation. PLoS Genet 7: e1001376 doi:10.1371/journal.pgen.1001376..

54. PaseroP, BensimonA, SchwobE (2002) Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus. Genes Dev 16: 2479–2484.

55. KwanEX, FossE, KruglyakL, BedalovA (2011) Natural polymorphism in BUL2 links cellular amino acid availability with chronological aging and telomere maintenance in yeast. PLoS Genet 7: e1002250 doi:10.1371/journal.pgen.1002250..

56. CubillosFA, LouisEJ, LitiG (2009) Generation of a large set of genetically tractable haploid and diploid Saccharomyces strains. FEMS Yeast Res 9: 1217–1225.

57. ChernoffYO, VincentA, LiebmanSW (1994) Mutations in eukaryotic 18S ribosomal RNA affect translational fidelity and resistance to aminoglycoside antibiotics. Embo J 13: 906–913.

58. KaeberleinM, PowersRW3rd, SteffenKK, WestmanEA, HuD, et al. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193–1196.

59. LindstromDL, LeverichCK, HendersonKA, GottschlingDE (2011) Replicative age induces mitotic recombination in the ribosomal RNA gene cluster of Saccharomyces cerevisiae. PLoS Genet 7: e1002015 doi:10.1371/journal.pgen.1002015..

60. KobayashiT, HeckDJ, NomuraM, HoriuchiT (1998) Expansion and contraction of ribosomal DNA repeats in Saccharomyces cerevisiae: requirement of replication fork blocking (Fob1) protein and the role of RNA polymerase I. Genes Dev 12: 3821–3830.

61. Brewer BJ, Raghuraman MK Preparation of Yeast DNA Embedded in Agarose Plugs. http://fangman-brewer.genetics.washington.edu/plug.html.

62. CherryJM, HongEL, AmundsenC, BalakrishnanR, BinkleyG, et al. (2012) Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res 40: D700–705.

63. Saccharomyces Genome Database. http://www.yeastgenome.org/.

64. Saccharomyces cerevisiae RM11-1a Sequencing Project. http://www.broadinstitute.org/annotation/genome/saccharomyces_cerevisiae/.

65. BrewerBJ, FangmanWL (1987) The localization of replication origins on ARS plasmids in S. cerevisiae. Cell 51: 463–471.

66. Brewer BJ, Raghuraman MK (2012) Yeast NIB-n-grab DNA prep for 2-D gels. http://fangman-brewergeneticswashingtonedu/nib-n-grabhtml: http://fangman-brewer.genetics.washington.edu/nib-n-grab.html.