Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase
Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.
Vyšlo v časopise:
Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003736
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003736
Souhrn
Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.
Zdroje
1. HanawaltPC (2007) Paradigms for the three rs: DNA replication, recombination, and repair. Mol Cell 28: 702–707.
2. LynchM (2010) Evolution of the mutation rate. Trends Genet 26: 345–352.
3. KirschnerM, GerhartJ (1998) Evolvability. Proc Natl Acad Sci U S A 95: 8420–8427.
4. HerrAJ, OgawaM, LawrenceNA, WilliamsLN, EggingtonJM, et al. (2011) Mutator suppression and escape from replication error-induced extinction in yeast. PLoS Genet 7: e1002282.
5. DrakeJW, CharlesworthB, CharlesworthD, CrowJF (1998) Rates of spontaneous mutation. Genetics 148: 1667–1686.
6. DaeeDL, MertzTM, ShcherbakovaPV (2010) A cancer-associated DNA polymerase delta variant modeled in yeast causes a catastrophic increase in genomic instability. Proc Natl Acad Sci U S A 107: 157–162.
7. DrakeJW, BebenekA, KisslingGE, PeddadaS (2005) Clusters of mutations from transient hypermutability. Proc Natl Acad Sci U S A 102: 12849–12854.
8. LoebLA (2011) Human cancers express mutator phenotypes: origin, consequences and targeting. Nat Rev Cancer 11: 450–457.
9. Nik-ZainalS, AlexandrovLB, WedgeDC, Van LooP, GreenmanCD, et al. (2012) Mutational Processes Molding the Genomes of 21 Breast Cancers. Cell 149: 979–993.
10. BielasJH, LoebKR, RubinBP, TrueLD, LoebLA (2006) Human cancers express a mutator phenotype. Proc Natl Acad Sci U S A 103: 18238–18242.
11. LoebLA, SpringgateCF, BattulaN (1974) Errors in DNA replication as a basis of malignant changes. Cancer Res 34: 2311–2321.
12. LoebLA (2001) A mutator phenotype in cancer. Cancer Res 61: 3230–3239.
13. RichardsB, ZhangH, PhearG, MeuthM (1997) Conditional mutator phenotypes in hMSH2-deficient tumor cell lines. Science 277: 1523–1526.
14. LoebLA (1997) Transient expression of a mutator phenotype in cancer cells. Science 277: 1449–1450.
15. MatsumotoY, MarusawaH, KinoshitaK, EndoY, KouT, et al. (2007) Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med 13: 470–476.
16. BurnsMB, LackeyL, CarpenterMA, RathoreA, LandAM, et al. (2013) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494: 366–370.
17. KnudsonAGJr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68: 820–823.
18. BergerAH, KnudsonAG, PandolfiPP (2011) A continuum model for tumour suppression. Nature 476: 163–169.
19. PavlovYI, ShcherbakovaPV (2010) DNA polymerases at the eukaryotic fork - 20 years later. Mutat Res 685: 45–53.
20. GordeninDA, Inge-VechtomovSG (1981) [Mechanism of mutant induction in the ade2 gene of diploid Saccharomyces cerevisiae yeasts by ultraviolet rays]. Genetika 17: 822–831.
21. Pavlov IuI, NoskovVN, Chernov IuO, GordeninDA (1988) [Mutability of LYS2 gene in diploid Saccharomyces yeasts. II. Frequency of mutants induced by 6-N-hydroxylaminopurine and propiolactone]. Genetika 24: 1752–1760.
22. TranHT, DegtyarevaNP, GordeninDA, ResnickMA (1999) Genetic factors affecting the impact of DNA polymerase delta proofreading activity on mutation avoidance in yeast. Genetics 152: 47–59.
23. KumarD, VibergJ, NilssonAK, ChabesA (2010) Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint. Nucleic Acids Res 38: 3975–3983.
24. KozminSG, SchaaperRM, ShcherbakovaPV, KulikovVN, NoskovVN, et al. (1998) Multiple antimutagenesis mechanisms affect mutagenic activity and specificity of the base analog 6-N-hydroxylaminopurine in bacteria and yeast. Mutat Res 402: 41–50.
25. MenezesMR, WaisertreigerIS, Lopez-BertoniH, LuoX, PavlovYI (2012) Pivotal role of inosine triphosphate pyrophosphatase in maintaining genome stability and the prevention of apoptosis in human cells. PLoS One 7: e32313.
26. ShcherbakovaPV, PavlovYI (1993) Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the URA3 gene of the yeast Saccharomyces cerevisiae. Mutagenesis 8: 417–421.
27. StepchenkovaEI, Koz'minSG, AleninVV, Pavlov IuI (2009) [Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae]. Genetika 45: 471–477.
28. ShcherbakovaPV, NoskovVN, PshenichnovMR, PavlovYI (1996) Base analog 6-N-hydroxylaminopurine mutagenesis in the yeast Saccharomyces cerevisiae is controlled by replicative DNA polymerases. Mutat Res 369: 33–44.
29. PavlovYI, SuslovVV, ShcherbakovaPV, KunkelTA, OnoA, et al. (1996) Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli: genetic control and molecular specificity. Mutat Res 357: 1–15.
30. BurgisNE, CunninghamRP (2007) Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase. J Biol Chem 282: 3531–3538.
31. RogozinIB, IyerLM, LiangL, GlazkoGV, ListonVG, et al. (2007) Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nat Immunol 8: 647–656.
32. SamaranayakeM, BujnickiJM, CarpenterM, BhagwatAS (2006) Evaluation of molecular models for the affinity maturation of antibodies: roles of cytosine deamination by AID and DNA repair. Chem Rev 106: 700–719.
33. ConticelloSG, LangloisMA, YangZ, NeubergerMS (2007) DNA deamination in immunity: AID in the context of its APOBEC relatives. Adv Immunol 94: 37–73.
34. LadaAG, IyerLM, RogozinIB, AravindL, Pavlov IuI (2007) [Vertebrate immunity: mutator proteins and their evolution]. Genetika 43: 1311–1327.
35. Teperek-TkaczM, PasqueV, GentschG, Ferguson-SmithAC (2011) Epigenetic reprogramming: is deamination key to active DNA demethylation? Reproduction 142: 621–632.
36. MaizelsN (2005) Immunoglobulin gene diversification. Annu Rev Genet 39: 23–46.
37. LadaAG, KrickCF, KozminSG, MayorovVI, KarpovaTS, et al. (2011) Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast. Biochemistry (Mosc) 76: 131–146.
38. Pavlov YI, Lange EK, Chromov-Borisov NN (1979) Studies on genetic activity of 6-hydroxylaminopurine and its riboside in strains of Salmonella typhimurium and Saccharomyces cerevisiae. Research of Biological Effects of Antropogenic Factors on Water Reservoirs. Irkutsk. pp. 11–30.
39. PavlovYI (1986) Mutants Highly Sensitive to the Mutagenic Action of 6-N-hydroxylaminopurine. Soviet Genetics 22: 2235–2243.
40. ModrichP (2006) Mechanisms in eukaryotic mismatch repair. J Biol Chem 281: 30305–30309.
41. NegishiK, LoakesD, SchaaperRM (2002) Saturation of DNA mismatch repair and error catastrophe by a base analogue in Escherichia coli. Genetics 161: 1363–1371.
42. RobertsSA, SterlingJ, ThompsonC, HarrisS, MavD, et al. (2012) Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell 46: 424–435.
43. KulikovVV, DerkatchIL, NoskovVN, TaruninaOV, ChernoffYO, et al. (2001) Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the LYS2 gene of yeast Saccharomyces cerevisiae. Mutat Res 473: 151–161.
44. TaylorBJ, Nik-ZainalS, WuYL, StebbingsLA, RaineK, et al. (2013) DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife 2: e00534.
45. LadaAG, DharA, BoissyRJ, HiranoM, RubelAA, et al. (2012) AID/APOBEC cytosine deaminase induces genome-wide kataegis. Biol Direct 7: 47.
46. HicksWM, KimM, HaberJE (2010) Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329: 82–85.
47. PoltoratskyV, HeacockM, KisslingGE, PrasadR, WilsonSH (2010) Mutagenesis dependent upon the combination of activation-induced deaminase expression and a double-strand break. Mol Immunol 48: 164–170.
48. StamatoyannopoulosJA, AdzhubeiI, ThurmanRE, KryukovGV, MirkinSM, et al. (2009) Human mutation rate associated with DNA replication timing. Nat Genet 41: 393–395.
49. ShcherbakovaPV, PavlovYI (1996) 3′→5′ exonucleases of DNA polymerases ε and δ correct base analog induced DNA replication errors on opposite DNA strands in Saccharomyces cerevisiae. Genetics 142: 717–726.
50. PavlovYI, NewlonCS, KunkelTA (2002) Yeast origins establish a strand bias for replicational mutagenesis. Mol Cell 10: 207–213.
51. WaisertreigerIS, ListonVG, MenezesMR, KimHM, LobachevKS, et al. (2012) Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools. Environ Mol Mutagen 53: 699–724.
52. WinzelerEA, ShoemakerDD, AstromoffA, LiangH, AndersonK, et al. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285: 901–906.
53. GiaeverG, ChuAM, NiL, ConnellyC, RilesL, et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387–391.
54. NishantKT, WeiW, ManceraE, ArguesoJL, SchlattlA, et al. (2010) The baker's yeast diploid genome is remarkably stable in vegetative growth and meiosis. PLoS Genet 6: e1001109 doi: 10.1371/journal.pgen.1001109
55. LynchM, SungW, MorrisK, CoffeyN, LandryCR, et al. (2008) A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc Natl Acad Sci U S A 105: 9272–9277.
56. Noskov V (1988) Studies of the mutagenic action of 6-N-hydroxylaminopurine and beta-propiolactone in diploid yeast Saccharomyces cerevisiae [Candidate of Biological Sciences]. Leningrad: Leningrad State University. 167 p.
57. HallBG (1990) Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 126: 5–16.
58. TorkelsonJ, HarrisRS, LombardoMJ, NagendranJ, ThulinC, et al. (1997) Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J 16: 3303–3311.
59. RoscheWA, FosterPL (1999) The role of transient hypermutators in adaptive mutation in Escherichia coli. Proc Natl Acad Sci U S A 96: 6862–6867.
60. FosterPL (2004) Adaptive mutation in Escherichia coli. J Bacteriol 186: 4846–4852.
61. TranHT, DegtyarevaNP, GordeninDA, ResnickMA (1999) Genetic factors affecting the impact of DNA polymerase δ proofreading activity on mutation avoidance in yeast. Genetics 152: 47–59.
62. LadaAG, WaisertreigerIS, GrabowCE, PrakashA, BorgstahlGE, et al. (2011) Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA. PLoS One 6: e24848.
63. BasuU, MengFL, KeimC, GrinsteinV, PefanisE, et al. (2011) The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144: 353–363.
64. AlexK, ShalekRS, AdiconisXian, GertnerRona S, et al. (2013) Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 498: 236–40.
65. EckertKA, SweasyJB (2012) DNA polymerases and their role in genomic stability. Environ Mol Mutagen 53: 643–684.
66. PhamP, BransteitterR, PetruskaJ, GoodmanMF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424: 103–107.
67. PhamP, CalabreseP, ParkSJ, GoodmanMF (2011) Analysis of a single-stranded DNA-scanning process in which activation-induced deoxycytidine deaminase (AID) deaminates C to U haphazardly and inefficiently to ensure mutational diversity. J Biol Chem 286: 24931–24942.
68. ChanK, SterlingJF, RobertsSA, BhagwatAS, ResnickMA, et al. (2012) Base damage within single-strand DNA underlies in vivo hypermutability induced by a ubiquitous environmental agent. PLoS Genet 8: e1003149.
69. ShcherbakovaPV, KunkelTA (1999) Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations. Mol Cell Biol 19: 3177–3183.
70. Sherman F. FG, Hick JB (1986) Methods in yeast genetics: Cold Spring Harbor Laboratory Press. 200 p.
71. OteroJM, VongsangnakW, AsadollahiMA, Olivares-HernandesR, MauryJ, et al. (2010) Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications. BMC Genomics 11: 723.
72. KelleyDR, SchatzMC, SalzbergSL (2010) Quake: quality-aware detection and correction of sequencing errors. Genome Biol 11: R116.
73. Drummond AJ AB, Buxton S, Cheung M, Cooper A, Duran C, et al.. (2012) Geneious v5.6, Available from http://www.geneious.com
74. CrooksGE, HonG, ChandoniaJM, BrennerSE (2004) WebLogo: a sequence logo generator. Genome Res 14: 1188–1190.
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