DNA, the central molecule of aging

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 786, Issue , 2016, Pages 1-7

  Lenart, Peter ^a   Krejci, Lumir ^a,b  

^a MASARYK UNIVERSITY   (Czech Republic)

^b ST ANNE S UNIVERSITY HOSPITAL   (Czech Republic)

Author keywords

Aging; Chromatin structure; DNA; DNA damage; DNA repair; Mutagenesis; Telomeres

Indexed keywords

DNA; TELOMERASE; CHROMATIN;

AGING; CHROMATIN STRUCTURE; DNA ADDUCT; DNA DAMAGE; DNA DETERMINATION; DNA METHYLATION; EXCISION REPAIR; GENE MUTATION; GENETIC ANALYSIS; HUMAN; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TELOMERE SHORTENING; CHEMISTRY; CHROMATIN; DNA REPAIR; GENETICS; PHYSIOLOGY; ULTRASTRUCTURE;

AGING; CHROMATIN; DNA; DNA DAMAGE; DNA REPAIR; HUMANS; TELOMERE SHORTENING;

EID: 84957106626     PISSN: 00275107     EISSN: 18792871     Source Type: Journal    
DOI: 10.1016/j.mrfmmm.2016.01.007     Document Type: Review

References (133)

1. Jin K. Modern biological theories of aging. Aging Dis. 2010, 1:72-74.
2. Trindade L.S., Aigaki T., Peixoto A.A., Balduino A., Mânica da Cruz I.B., Heddle J.G. A novel classification system for evolutionary aging theories. Front Genet. 2013, 4.
3. Burtner C.R., Kennedy B.K. Progeria syndromes and ageing: what is the connection?. Nat. Rev. Mol. Cell Biol. 2010, 11:567-578.
4. Freitas A.A., Vasieva O., de Magalhães J.P A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related. BMC Genomics 2011, 12:27.
5. O'sullivan R.J., Kubicek S., Schreiber S.L., Karlseder J. Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres. Nat. Struct. Mol. Biol. 2010, 17:1218-1225.
6. Bodnar A.G., Ouellette M., Frolkis M., Holt S.E., Chiu C.P., Morin G.B., et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998, 279:349-352.
7. Sedelnikova O.A., Horikawa I., Zimonjic D.B., Popescu N.C., Bonner W.M., Barrett J.C. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat. Cell Biol. 2004, 6:168-170.
8. Feser J., Truong D., Das C., Carson J.J., Kieft J., Harkness T., et al. Elevated histone expression promotes life span extension. Mol. Cell 2010, 39:724-735.
9. White R.R., Milholland B., de Bruin A., Curran S., Laberge R.-M., van Steeg H., et al. Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing. Nat. Commun. 2015, 6.
10. Mozgová I., Mokroš P., Fajkus J. Dysfunction of chromatin assembly factor 1 induces shortening of telomeres and loss of 45S rDNA in Arabidopsis thaliana[W][OA]. Plant Cell 2010, 22:2768-2780.
11. Falk M., Lukášová E., Kozubek S. Chromatin structure influences the sensitivity of DNA to -radiation. Biochim. Biophys. Acta BBA: Mol. Cell Res. 2008, 1783:2398-2414.
12. Li B., Carey M., Workman J.L. The role of chromatin during transcription. Cell 2007, 128:707-719.
13. Oberdoerffer P., Michan S., McVay M., Mostoslavsky R., Vann J., Park S.-K., et al. DNA damage-induced alterations in chromatin contribute to genomic integrity and age-related changes in gene expression. Cell 2008, 135:907-918.
14. Oikawa S., Kawanishi S. Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett. 1999, 453:365-368.
15. Luger K., Mäder A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 1997, 389:251-260.
16. Hu Z., Chen K., Xia Z., Chavez M., Pal S., Seol J.-H., et al. Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging: Genes Dev 2014;28:396-408. telomeres. Nat. Struct. Mol. Biol. 2010, 17:1218-1225.
17. Ivanov A., Pawlikowski J., Manoharan I., van Tuyn J., Nelson D.M., Rai T.S., et al. Lysosome-mediated processing of chromatin in senescence. J. Cell Biol. 2013, 202:129-143.
18. Lesur I., Campbell J.L. The transcriptome of prematurely aging yeast cells is similar to that of telomerase-deficient cells. Mol. Biol. Cell 2004, 15:1297-1312.
19. Kouzarides T. Chromatin modifications and their function. Cell 2007, 128:693-705.
20. Dang W., Steffen K.K., Perry R., Dorsey J.A., Johnson F.B., Shilatifard A., et al. Histone H4 lysine-16 acetylation regulates cellular lifespan. Nature 2009, 459:802-807.
21. Shogren-Knaak M., Ishii H., Sun J.-M., Pazin M.J., Davie J.R., Peterson C.L. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 2006, 311:844-847.
22. Zhou B.-R., Feng H., Ghirlando R., Kato H., Gruschus J., Bai Y. Histone H4 K16Q mutation, an acetylation mimic, causes structural disorder of its N-terminal basic patch in the nucleosome. J. Mol. Biol. 2012, 421:30-37.
23. Sinclair D.A., Guarente L. Extrachromosomal rDNA circles- a cause of aging in yeast. Cell 1997, 91:1033-1042.
24. Tissenbaum H.A., Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001, 410:227-230.
25. Rogina B., Helfand S.L. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl.Acad. Sci. U. S. A 2004, 101:15998-16003.
26. Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol. Cell 2004, 16:93-105.
27. Pruitt K., Zinn R.L., Ohm J.E., McGarvey K.M., Kang S.-H.L., Watkins D.N., et al. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet. 2006, 2.
28. Herranz D., Muñoz-Martin M., Cañamero M., Mulero F., Martinez-Pastor B., Fernandez-Capetillo O., et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 2010, 1:3.
29. Satoh A., Brace C.S., Rensing N., Clifton P., Wozniak D.F., Herzog E.D., et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013, 18:416-430.
30. Igarashi K., Kashiwagi K. Modulation of cellular function by polyamines. Int. J. Biochem. Cell Biol. 2010, 42:39-51.
31. Flamigni F., Stanic' I., Facchini A., Cetrullo S., Tantini B., Borzì R.M., et al. Polyamine biosynthesis as a target to inhibit apoptosis of non-tumoral cells. Amino Acids 2007, 33:197-202.
32. Gerner E.W., Meyskens F.L. Polyamines and cancer: old molecules, new understanding. Nat. Rev. Cancer 2004, 4:781-792.
33. Eisenberg T., Knauer H., Schauer A., Büttner S., Ruckenstuhl C., Carmona-Gutierrez D., et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 2009, 11:1305-1314.
34. Greer E.L., Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat. Rev. Genet. 2012, 13:343-357.
35. Santos-Rosa H., Schneider R., Bannister A.J., Sherriff J., Bernstein B.E., Emre N.C.T., et al. Active genes are tri-methylated at K4 of histone H3. Nature 2002, 419:407-411.
36. Shah P.P., Donahue G., Otte G.L., Capell B.C., Nelson D.M., Cao K., et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 2013, 27:1787-1799.
37. Sun D., Luo M., Jeong M., Rodriguez B., Xia Z., Hannah R., et al. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell 2014, 14:673-688.
38. Greer E.L., Maures T.J., Hauswirth A.G., Green E.M., Leeman D.S., Maro G.S., et al. Members of the histone H3 lysine 4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 2010, 466:383-387.
39. Maures T.J., Greer E.L., Hauswirth A.G., Brunet A. H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline indipedent, insulin-dependent, manner. Aging Cell 2011, 10:980-990.
40. Siebold A.P., Banerjee R., Tie F., Kiss D.L., Moskowitz J., Harte P.J. Polycomb repressive complex 2 and trithorax modulate drosophila longevity and stress resistance. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:169-174.
41. Rhie B.H., Song Y., Ryu H., Ahn S.H. Cellular aging is associated with increased ubiquitylation of histone H2B in yeast telomeric heterochromatin. Biochem. Biophys. Res. Commun. 2013, 439:570-575.
42. Hashimshony T., Zhang J., Keshet I., Bustin M., Cedar H. The role of DNA methylation in setting up chromatin structure during development. Nat. Genet. 2003, 34:187-192.
43. Gilbert N., Thomson I., Boyle S., Allan J., Ramsahoye B., Bickmore W.A. DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction. J. Cell Biol. 2007, 177:401-411.
44. Deaton A.M., Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011, 25:1010-1022.
45. Ting A.H., McGarvey K.M., Baylin S.B. The cancer epigenome-components and functional correlates. Genes Dev. 2006, 20:3215-3231.
46. Sproul D., Meehan R.R. Genomic insights into cancer-associated aberrant CpG island hypermethylation. Brief. Funct. Genomics 2013, 12:174-190.
47. Hon G.C., Hawkins R.D., Caballero O.L., Lo C., Lister R., Pelizzola M., et al. Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res. 2012, 22:246-258.
48. Cruickshanks H.A., McBryan T., Nelson D.M., VanderKraats N.D., Shah P.P., van Tuyn J., et al. Senescent cells harbour features of the cancer epigenome. Nat. Cell Biol. 2013, 15:1495-1506.
49. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013, 14:R115.
50. Hannum G., Guinney J., Zhao L., Zhang L., Hughes G., Sadda S., et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 2013, 49:359-367.
51. Weidner C.I., Lin Q., Koch C.M., Eisele L., Beier F., Ziegler P., et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol. 2014, 15:R24.
52. Marioni R.E., Shah S., McRae A.F., Chen B.H., Colicino E., Harris S.E., et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015, 16.
53. Lee B.C., Kaya A., Ma S., Kim G., Gerashchenko M.V., Yim S.H., et al. Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status. Nat. Commun. 2014, 5:3592.
54. Zimmerman J.A., Malloy V., Krajcik R., Orentreich N. Nutritional control of aging. Exp. Gerontol. 2003, 38:47-52.
55. Miller R.A., Buehner G., Chang Y., Harper J.M., Sigler R., Smith-Wheelock M. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 2005, 4:119-125.
56. Sun L., Sadighi Akha A.A., Miller R.A., Harper J.M. Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J. Gerontol. A: Biol. Sci. Med. Sci. 2009, 64A:711-722.
57. Kozieł R., Ruckenstuhl C., Albertini E., Neuhaus M., Netzberger C., Bust M., et al. Methionine restriction slows down senescence in human diploid fibroblasts. Aging Cell 2014, 13:1038-1048.
58. Sanchez-Roman I., Gomez A., Gomez J., Suarez H., Sanchez C., Naudi A., et al. Forty percent methionine restriction lowers DNA methylation, complex I ROS generation, and oxidative damage to mtDNA and mitochondrial proteins in rat heart. J. Bioenerg. Biomembr. 2011, 43:699-708.
59. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005, 19:2100-2110.
60. Hiyama E., Hiyama K. Telomere and telomerase in stem cells. Br. J. Cancer 2007, 96:1020-1024.
61. Steinert S., Shay J.W., Wright W.E. Transient expression of human telomerase extends the life span of normal human fibroblasts. Biochem. Biophys. Res. Commun. 2000, 273:1095-1098.
62. Blasco M.A., Lee H.-W., Hande M.P., Samper E., Lansdorp P.M., DePinho R.A., et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997, 91:25-34.
63. Farazi P.A., Glickman J., Horner J., DePinho R.A. Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res. 2006, 66:4766-4773.
64. Lee H.-W., Blasco M.A., Gottlieb G.J., Horner J.W., Greider C.W., DePinho R.A. Essential role of mouse telomerase in highly proliferative organs. Nature 1998, 392:569-574.
65. Du X., Shen J., Kugan N., Furth E.E., Lombard D.B., Cheung C., et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol. Cell Biol. 2004, 24:8437-8446.
66. Change S., Multani A.S., Cabrera N.G., Naylor M.L., Laud P., Lombard D., et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat. Genet. 2004, 36:877-882.
67. Yu C.E., Oshima J., Fu Y.H., Wijsman E.M., Hisama F., Alisch R., et al. Positional cloning of the Werner's syndrome gene. Science 1996, 272:258-262.
68. Artandi S.E., Alson S., Tietze M.K., Sharpless N.E., Ye S., Greenberg R.A., et al. Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc. Natl. Acad. Sci. 2002, 99:8191-8196.
69. Canela A., Martín-Caballero J., Flores J.M., Blasco M.A. Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-tert mice. Mol. Cell Biol. 2004, 24:4275-4293.
70. Rafnar T., Sulem P., Stacey S.N., Geller F., Gudmundsson J., Sigurdsson A., et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet. 2009, 41:221-227.
71. Tomás-Loba A., Flores I., Fernández-Marcos P.J., Cayuela M.L., Maraver A., Tejera A., et al. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 2008, 135:609-622.
72. Bernardes de Jesus B., Vera E., Schneeberger K., Tejera A.M., Ayuso E., Bosch F., et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 2012, 4:691-704.
73. Gorbunova V., Seluanov A. Coevolution of telomerase activity and body mass in mammals: from mice to beavers. Mech. Ageing Dev. 2009, 130:3-9.
74. Gomes N.M.V., Ryder O.A., Houck M.L., Charter S.J., Walker W., Forsyth N.R., et al. Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 2011, 10:761-768.
75. Heidinger B.J., Blount J.D., Boner W., Griffiths K., Metcalfe N.B., Monaghan P. Telomere length in early life predicts lifespan. Proc. Natl. Acad. Sci. 2012, 109:1743-1748.
76. Cawthon R.M., Smith K.R., O'Brien E., Sivatchenko A., Kerber R.A. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 2003, 361:393-395.
77. Njajou O.T., Hsueh W.-C., Blackburn E.H., Newman A.B., Wu S.-H., Li R., et al. Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J. Gerontol. A: Biol. Sci. Med. Sci. 2009, 64A:860-864.
78. Wentzensen I.M., Mirabello L., Pfeiffer R.M., Savage S.A. The association of telomere length and cancer: a meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2011, 20:1238-1250.
79. Zhang W., Wang Y., Hou K., Jia L.-P., Ma J., Zhao D.-L., et al. A correlation study of telomere length in peripheral blood leukocytes and kidney function with age. Mol. Med. Rep. 2015.
80. Li Z., Tang J., Li H., Chen S., He Y., Liao Y., et al. Shorter telomere length in peripheral blood leukocytes is associated with childhood autism. Sci. Rep. 2014, 4.
81. Lee J., Sandford A.J., Connett J.E., Yan J., Mui T., Li Y., et al. The relationship between telomere length and mortality in chronic obstructive pulmonary disease [COPD]. PLoS One 2012, 7:e35567.
82. Machiela M.J., Hsiung C.A., Shu X.-O., Seow W.J., Wang Z., Matsuo K., et al. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia. Int. J. Cancer 2014, n/a -n/a.
83. Jones A.M., Beggs A.D., Carvajal-Carmona L., Farrington S., Tenesa A., Walker M., et al. TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres. Gut 2012, 61:248-254.
84. Gramatges M.M., Telli M.L., Balise R., Ford J.M. Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol. Biomarkers Prev. 2010, 19:605-613.
85. Cabelof D.C., Yanamadala S., Raffoul J.J., Guo Z., Soofi A., Heydari A.R. Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline. DNA Repair 2003, 2:295-307.
86. Guo Z., Heydari A., Richardson A. Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: effect of age and dietary restriction. Exp. Cell Res. 1998, 245:228-238.
87. Um J.H., Kim S.J., Kim D.W., Ha M.Y., Jang J.H., Kim D.W., et al. Tissue-specific changes of DNA repair protein Ku and mtHSP70 in aging rats and their retardation by caloric restriction. Mech. Ageing Dev. 2003, 124:967-975.
88. Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004, 305:390-392.
89. Civitarese A.E., Carling S., Heilbronn L.K., Hulver M.H., Ukropcova B., Deutsch W.A., et al. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 2007, 4.
90. Palacios J.A., Herranz D., De Bonis M.L., Velasco S., Serrano M., Blasco M.A. SIRT1 contributes to telomere maintenance and augments global homologous recombination. J. Cell Biol. 2010, 191:1299-1313.
91. Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., et al. Rapamycin fed late in life extends lifespan in genetically heterogenous mice. Nature 2009, 460:392-395.
92. Dao V., Pandeswara S., Liu Y., Hurez V., Dodds S., Callaway D., et al. Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage. Cancer Prev. Res. 2015, 8:400-409.
93. Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat. Res. 1997, 387:147-163.
94. Stuart J.A., Bourque B.M., de Souza-Pinto N.C., Bohr V.A. No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient in removal of 8-oxodeoxyguanine from mitochondrial DNA. Free Radic. Biol. Med. 2005, 38:737-745.
95. Atamna H., Cheung I., Ames B.N. A method for detecting abasic sites in living cells: age-dependent changes in base excision repair. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:686-691.
96. Maclean M.J., Aamodt R., Harris N., Alseth I., Seeberg E., Bjørås M., et al. Base excision repair activities required for yeast to attain a full chronological life span. Aging Cell 2003, 2:93-104.
97. Caldecott K.W. Single-strand break repair and genetic disease. Nat. Rev. Genet. 2008, 9:619-631.
98. Fu C.S., Harris S.B., Wilhelmi P., Walford R.L. Lack of effect of age and dietary restriction on DNA single-stranded breaks in brain, liver, and kidney of [C3H × C57BL/10]F1 Mice. J. Gerontol. 1991, 46:B78-80.
99. Trzeciak A.R., Mohanty J.G., Jacob K.D., Barnes J., Ejiogu N., Lohani A., et al. Oxidative damage to DNA and single strand break repair capacity: relationship to other measures of oxidative stress in a population cohort. Mutat. Res. Mol. Mech. Mutagen. 2012, 736:93-103.
100. Li H., Mitchell J.R., Hasty P. DNA double-strand breaks: a potential causative factor for mammalian aging. Mech. Ageing Dev. 2008, 129:416-424.
101. Singh N.P., Ogburn C.E., Wolf N.S., van Belle G., Martin G.M. DNA double-strand breaks in mouse kidney cells with age. Biogerontology 2001, 2:261-270.
102. Sedelnikova O.A., Horikawa I., Redon C., Nakamura A., Zimonjic D.B., Popescu N.C., et al. Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell 2008, 7:89-100.
103. Ward I.M., Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J. Biol. Chem. 2001, 276:47759-47762.
104. Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem. 2001, 276:42462-42467.
105. Downs J.A., Allard S., Jobin-Robitaille O., Javaheri A., Auger A., Bouchard N., et al. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol, Cell 2004, 16:979-990.
106. Rogakou E.P., Boon C., Redon C., Bonner W.M. Megabase chromatin domains involved in DNA double-strand breaks in Vivo. J. Cell Biol. 1999, 146:905-916.
107. Zhang Y., Griffin K., Mondal N., Parvin J.D. Phosphorylation of histone H2A inhibits transcription on chromatin templates. J. Biol. Chem. 2004, 279:21866-21872.
108. Solovjeva L.V., Svetlova M.P., Chagin V.O., Tomilin N.V. Inhibition of transcription at radiation-induced nuclear foci of phosphorylated histone H2AX in mammalian cells. Chromosome Res. 2007, 15:787-797.
109. Di Micco R., Sulli G., Dobreva M., Liontos M., Botrugno O.A., Gargiulo G., et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat. Cell Biol. 2011, 13:292-302.
110. Goodarzi A.A., Jeggo P., Lobrich M. The influence of heterochromatin on DNA double strand break repair: getting the strong, silent type to relax. DNA Repair 2010, 9:1273-1282.
111. Giunta S., Belotserkovskaya R., Jackson S.P. DNA damage signaling in response to double-strand breaks during mitosis. J. Cell Biol. 2010, 190:197-207.
112. Bakkenist C.J., Kastan M.B. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003, 421:499-506.
113. Bencokova Z., Kaufmann M.R., Pires I.M., Lecane P.S., Giaccia A.J., Hammond E.M. ATM activation and signaling under hypoxic conditions. Mol. Cell Biol. 2009, 29:526-537.
114. Bekker-Jensen S., Mailand N. The ubiquitin- and SUMO-dependent signaling response to DNA double-strand breaks. FEBS Lett. 2011, 585:2914-2919.
115. Moyal L., Lerenthal Y., Gana-Weisz M., Mass G., So S., Wang S.-Y., et al. Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol. Cell 2011, 41:529-542.
116. Shi L., Oberdoerffer P. Chromatin dynamics in DNA double-strand break repair. Biochim. Biophys. Acta 2012, 1819:811-819.
117. Tamburini B.A., Tyler J.K. Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair. Mol. Cell Biol. 2005, 25:4903-4913.
118. Haigis M.C., Sinclair D.A. Mammalian Sirtuins: biological insights and disease relevance. Annu. Rev. Pathol. 2010, 5:253-295.
119. Tennen R.I., Bua D.J., Wright W.E., Chua K.F. SIRT6 is required for maintenance of telomere position effect in human cells. Nat. Commun. 2011, 2:433.
120. Mostoslavsky R., Chua K.F., Lombard D.B., Pang W.W., Fischer M.R., Gellon L., et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 2006, 124:315-329.
121. Chen C., Jomaa A., Ortega J., Alani E.E. Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:E44-E53.
122. Qian H., Xu X., Niklason L.E. PCH-2 regulates Caenorhabditis elegans lifespan. Aging 2015, 7:1-11.
123. Schaetzlein S., Kodandaramireddy N., Ju Z., Lechel A., Stepzynska A., Lilli D.R., et al. Exo1 deletion impairs DNA damage signal induction and prolongs lifespan of telomere dysfunctional mice. Cell 2007, 130:863-877.
124. Failla G. The aging process and cancerogenesis. Ann. N. Y. Acad. Sci. 1958, 71:1124-1140.
125. Szilard L. On the nature of the aging process. Proc. Natl. Acad. Sci. U. S. A. 1959, 45:30-45.
126. Dollé M.E.T., Giese H., Hopkins C.L., Martus H.-J., Hausdorff J.M., Vijg J. Rapid accumulation of genome rearrangements in liver but not in brain of old mice. Nat. Genet. 1997, 17:431-434.
127. Dollé M.E.T., Snyder W.K., Gossen J.A., Lohman P.H.M., Vijg J. Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:8403-8408.
128. Vijg J., Dollé M.E.T. Large genome rearrangements as a primary cause of aging. Mech. Ageing Dev. 2002, 123:907-915.
129. Narayanan L., Fritzell J.A., Baker S.M., Liskay R.M., Glazer P.M. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair genePms2. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:3122-3127.
130. Busuttil R.A., Garcia A.M., Cabrera C., Rodriquez A., Suh Y., Kim W.H., et al. Organspecific increase in mutation accumulation and apoptosis rate in CuZn-superoxide dismutase-deficient mice. Cancer Res. 2005, 65:11271-11275.
131. Dollé M.E.T., Busuttil R.A., Garcia A.M., Wijnhoven S., van Drunen E., Niedernhofer L.J., et al. Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice. Mutat. Res. 2006, 596:22-35.
132. Kaya A., Lobanov A.V., Gladyshev V.N. Evidence that mutation accumulation does not cause aging in Saccharomyces cerevisiae. Aging Cell 2015, 14:366-371.
133. Goldman D.P., Cutler D., Rowe J.W., Michaud P.-C., Sullivan J., Peneva D., et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff. [Millwood] 2013, 32:1698-1705.