Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres

English version České info

8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1)–initiated DNA base excision repair (BER). Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere–FISH), by chromosome orientation–FISH (CO–FISH), and by indirect immunofluorescence in combination with telomere–FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1^−/−) mouse tissues and primary embryonic fibroblasts (MEFs) cultivated in hypoxia condition (3% oxygen), whereas telomere shortening was detected in Ogg1^−/− mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen) or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1^−/− mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1^−/− mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1^−/− MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity in mammals.

Vyšlo v časopise: Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres. PLoS Genet 6(5): e32767. doi:10.1371/journal.pgen.1000951
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000951

Souhrn

Zdroje

1. BlackburnEH

2001 Switching and signaling at the telomere. Cell 106 661 673

2. d'Adda di FagagnaF

TeoSH

JacksonSP

2004 Functional links between telomeres and proteins of the DNA-damage response. Genes Dev 18 1781 1799

3. de LangeT

2005 Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19 2100 2110

4. van SteenselB

de LangeT

1997 Control of telomere length by the human telomeric protein TRF1. Nature 385 740 743

5. SmithS

de LangeT

2000 Tankyrase promotes telomere elongation in human cells. Curr Biol 10 1299 1302

6. LoayzaD

De LangeT

2003 POT1 as a terminal transducer of TRF1 telomere length control. Nature 423 1013 1018

7. ShoreD

BianchiA

2009 Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase. Embo J 28 2309 2322

8. KarlsederJ

SmogorzewskaA

de LangeT

2002 Senescence induced by altered telomere state, not telomere loss. Science 295 2446 2449

9. HockemeyerD

SfeirAJ

ShayJW

WrightWE

de LangeT

2005 POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end. Embo J 24 2667 2678

10. WuL

MultaniAS

HeH

Cosme-BlancoW

DengY

2006 Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126 49 62

11. DenchiEL

de LangeT

2007 Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448 1068 1071

12. GuoX

DengY

LinY

Cosme-BlancoW

ChanS

2007 Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. Embo J 26 4709 4719

13. van SteenselB

SmogorzewskaA

de LangeT

1998 TRF2 protects human telomeres from end-to-end fusions. Cell 92 401 413

14. ZhuXD

NiedernhoferL

KusterB

MannM

HoeijmakersJH

2003 ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 12 1489 1498

15. CelliGB

DenchiEL

de LangeT

2006 Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol 8 885 890

16. CrabbeL

VerdunRE

HaggblomCI

KarlsederJ

2004 Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306 1951 1953

17. AtanasiuC

DengZ

WiedmerA

NorseenJ

LiebermanPM

2006 ORC binding to TRF2 stimulates OriP replication. EMBO Rep 7 716 721

18. TatsumiY

EzuraK

YoshidaK

YugawaT

Narisawa-SaitoM

2008 Involvement of human ORC and TRF2 in pre-replication complex assembly at telomeres. Genes Cells 13 1045 1059

19. SfeirA

KosiyatrakulST

HockemeyerD

MacRaeSL

KarlsederJ

2009 Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138 90 103

20. von ZglinickiT

PetrieJ

KirkwoodTB

2003 Telomere-driven replicative senescence is a stress response. Nat Biotechnol 21 229 230

21. RubioMA

DavalosAR

CampisiJ

2004 Telomere length mediates the effects of telomerase on the cellular response to genotoxic stress. Exp Cell Res 298 17 27

22. von ZglinickiT

PilgerR

SitteN

2000 Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic Biol Med 28 64 74

23. HenleES

HanZ

TangN

RaiP

LuoY

1999 Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. J Biol Chem 274 962 971

24. OikawaS

KawanishiS

1999 Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett 453 365 368

25. OikawaS

Tada-OikawaS

KawanishiS

2001 Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening. Biochemistry 40 4763 4768

26. OpreskoPL

FanJ

DanzyS

WilsonDM3rd

BohrVA

2005 Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic Acids Res 33 1230 1239

27. DizdarogluM

KirkaliG

JarugaP

2008 Formamidopyrimidines in DNA: mechanisms of formation, repair, and biological effects. Free Radic Biol Med 45 1610 1621

28. MemisogluA

SamsonL

2000 Base excision repair in yeast and mammals. Mutat Res 451 39 51

29. HuJ

de Souza-PintoNC

HaraguchiK

HogueBA

JarugaP

2005 Repair of formamidopyrimidines in DNA involves different glycosylases: role of the OGG1, NTH1, and NEIL1 enzymes. J Biol Chem 280 40544 40551

30. AkbariM

KrokanHE

2008 Cytotoxicity and mutagenicity of endogenous DNA base lesions as potential cause of human aging. Mech Ageing Dev 129 353 365

31. HegdeML

HazraTK

MitraS

2008 Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 18 27 47

32. MichaelsML

CruzC

GrollmanAP

MillerJH

1992 Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. Proc Natl Acad Sci U S A 89 7022 7025

33. GrollmanAP

MoriyaM

1993 Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet 9 246 249

34. BoiteuxS

RadicellaJP

1999 Base excision repair of 8-hydroxyguanine protects DNA from endogenous oxidative stress. Biochimie 81 59 67

35. NakabeppuY

SakumiK

SakamotoK

TsuchimotoD

TsuzukiT

2006 Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biol Chem 387 373 379

36. KlunglandA

RosewellI

HollenbachS

LarsenE

DalyG

1999 Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci U S A 96 13300 13305

37. XieY

YangH

CunananC

OkamotoK

ShibataD

2004 Deficiencies in mouse Myh and Ogg1 result in tumor predisposition and G to T mutations in codon 12 of the K-ras oncogene in lung tumors. Cancer Res 64 3096 3102

38. KunisadaM

SakumiK

TominagaY

BudiyantoA

UedaM

2005 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. Cancer Res 65 6006 6010

39. NakabeppuY

TsuchimotoD

FuruichiM

SakumiK

2004 The defense mechanisms in mammalian cells against oxidative damage in nucleic acids and their involvement in the suppression of mutagenesis and cell death. Free Radic Res 38 423 429

40. OkaS

OhnoM

TsuchimotoD

SakumiK

FuruichiM

2008 Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs. Embo J 27 421 432

41. XieY

YangH

MillerJH

ShihDM

HicksGG

2008 Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G2/M arrest and multinucleation. Carcinogenesis 29 722 728

42. de Souza-PintoNC

EideL

HogueBA

ThyboT

StevnsnerT

2001 Repair of 8-oxodeoxyguanosine lesions in mitochondrial dna depends on the oxoguanine dna glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial dna of OGG1-defective mice. Cancer Res 61 5378 5381

43. RuferN

DragowskaW

ThornburyG

RoosnekE

LansdorpPM

1998 Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol 16 743 747

44. ZijlmansJM

MartensUM

PoonSS

RaapAK

TankeHJ

1997 Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats. Proc Natl Acad Sci U S A 94 7423 7428

45. WangY

ErdmannN

GiannoneRJ

WuJ

GomezM

2005 An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres. Proc Natl Acad Sci U S A 102 10256 10260

46. GomezM

WuJ

SchreiberV

DunlapJ

DantzerF

2006 PARP1 is a TRF2-associated poly(ADP-ribose)polymerase and protects eroded telomeres. Mol Biol Cell 17 1686 1696

47. BaileySM

BrennemanMA

GoodwinEH

2004 Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res 32 3743 3751

48. KrukPA

RampinoNJ

BohrVA

1995 DNA damage and repair in telomeres: relation to aging. Proc Natl Acad Sci U S A 92 258 262

49. AskreeSH

YehudaT

SmolikovS

GurevichR

HawkJ

2004 A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl Acad Sci U S A 101 8658 8663

50. LuJ

LiuY

2010 Deletion of Ogg1 DNA glycosylase results in telomere base damage and length alteration in yeast. Embo J 29 398 409

51. de Souza-PintoNC

MaynardS

HashiguchiK

HuJ

MuftuogluM

2009 The Recombination Protein Rad52 Cooperates with the Excision Repair Protein Ogg1 for the Repair of Oxidative Lesions in Mammalian Cells. Mol Cell Biol 29 4441 4454

52. LomaxME

CunniffeS

O'NeillP

2004 8-OxoG retards the activity of the ligase III/XRCC1 complex during the repair of a single-strand break, when present within a clustered DNA damage site. DNA Repair (Amst) 3 289 299

53. ParsonsJL

ZharkovDO

DianovGL

2005 NEIL1 excises 3′ end proximal oxidative DNA lesions resistant to cleavage by NTH1 and OGG1. Nucleic Acids Res 33 4849 4856

54. MourguesS

LomaxME

O'NeillP

2007 Base excision repair processing of abasic site/single-strand break lesions within clustered damage sites associated with XRCC1 deficiency. Nucleic Acids Res 35 7676 7687

55. ThompsonLH

WestMG

2000 XRCC1 keeps DNA from getting stranded. Mutat Res 459 1 18

56. d'Adda di FagagnaF

ReaperPM

Clay-FarraceL

FieglerH

CarrP

2003 A DNA damage checkpoint response in telomere-initiated senescence. Nature 426 194 198

57. TakaiH

SmogorzewskaA

de LangeT

2003 DNA damage foci at dysfunctional telomeres. Curr Biol 13 1549 1556

58. CrabbeL

JauchA

NaegerCM

Holtgreve-GrezH

KarlsederJ

2007 Telomere dysfunction as a cause of genomic instability in Werner syndrome. Proc Natl Acad Sci U S A 104 2205 2210

59. SahariaA

GuittatL

CrockerS

LimA

SteffenM

2008 Flap endonuclease 1 contributes to telomere stability. Curr Biol 18 496 500

60. YoshiokaY

KitagawaY

TakanoY

YamaguchiK

NakamuraT

1999 Experimental and Theoretical Studies on the Selectivity of GGG Triplets toward One-Electron Oxidation in B-Form DNA. J Am Chem Soc 121 8712 8719

61. SaitoI

NakamuraI

NakataniK

1998 Mapping of the Hot Spots for DNA Damage by One-Electron Oxidation: Efficacy of GG Doublets and GGG Triplets as a Trap in Long-Range Hole Migration. J Am Chem Soc 120 12686 12687

62. KawanishiS

OikawaS

MurataM

TsukitomeH

SaitoI

1999 Site-specific oxidation at GG and GGG sequences in double-stranded DNA by benzoyl peroxide as a tumor promoter. Biochemistry 38 16733 16739

63. BrevetV

BerthiauAS

CivitelliL

DoniniP

SchramkeV

2003 The number of vertebrate repeats can be regulated at yeast telomeres by Rap1-independent mechanisms. Embo J 22 1697 1706

64. PawarV

JingjingL

PatelN

KaurN

DoetschPW

2009 Checkpoint kinase phosphorylation in response to endogenous oxidative DNA damage in repair-deficient stationary-phase Saccharomyces cerevisiae. Mech Ageing Dev 130 501 508

65. CarsonMJ

HartwellL

1985 CDC17: an essential gene that prevents telomere elongation in yeast. Cell 42 249 257

66. AdamsAK

HolmC

1996 Specific DNA replication mutations affect telomere length in Saccharomyces cerevisiae. Mol Cell Biol 16 4614 4620

67. VartanianV

LowellB

MinkoIG

WoodTG

CeciJD

2006 The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc Natl Acad Sci U S A 103 1864 1869

68. SwansonRL

MoreyNJ

DoetschPW

Jinks-RobertsonS

1999 Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae. Mol Cell Biol 19 2929 2935