Persistent γH2AX: A promising molecular marker of DNA damage and aging

Mutation Research - Reviews in Mutation Research

Volumn 766, Issue , 2015, Pages 1-19

  Siddiqui, Mohammad Sabbir ^a,b   François, Maxime ^a   Fenech, Michael F ^a   Leifert, Wayne R ^a  

^a CSIRO   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Aging; DNA damage; Ionizing radiation; H2AX

Indexed keywords

ANTIINFECTIVE AGENT; GAMMA HISTONE H2AX; HISTONE H2AX; MOLECULAR MARKER; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; H2AFX PROTEIN, HUMAN; HISTONE;

AGING; BRAIN TISSUE; CANCER RADIOTHERAPY; CHEEK CELL; CHRONIC DISEASE; DNA DAMAGE; DROSOPHILA; FIBROBLAST; FLUORESCENCE MICROSCOPY; GERM CELL; HUMAN; IONIZING RADIATION; LIVER; LONG TERM CARE; MINIPIG; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PUPA; RETROSPECTIVE STUDY; REVIEW; SENESCENCE; SKIN BIOPSY; SPINAL CORD; SYRIAN HAMSTER; TELOMERE; TREATMENT RESPONSE; GENETICS; METABOLISM; PHYSIOLOGY;

AGING; BIOMARKERS; DNA DAMAGE; HISTONES; HUMANS;

EID: 84947617075     PISSN: 13835742     EISSN: 13882139     Source Type: Journal    
DOI: 10.1016/j.mrrev.2015.07.001     Document Type: Review

References (186)

1. Dugle D.L., Gillespie C.J., Chapman J.D. DNA strand breaks, repair, and survival in x-irradiated mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 1976, 73:809-812.
2. Olive P.L. The role of DNA single- and double-strand breaks in cell killing by ionizing radiation. Radiat. Res. 1998, 150:S42-S51.
3. Mah L.J., El-Osta A., Karagiannis T.C. gammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 2010, 24:679-686.
4. Sharpless N.E., DePinho R.A. How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 2007, 8:703-713.
5. Ward I., Chen J. Early events in the DNA damage response. Curr. Top. Dev. Biol. 2004, 63:1-35.
6. Rogakou E.P., Pilch D.R., Orr A.H., Ivanova V.S., Bonner W.M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 1998, 273:5858-5868.
7. Savic V., Yin B., Maas N.L., Bredemeyer A.L., Carpenter A.C., Helmink B.A., Yang-Iott K.S., Sleckman B.P., Bassing C.H. Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol. Cell 2009, 34:298-310.
8. Redon C., Pilch D., Rogakou E., Sedelnikova O., Newrock K., Bonner W. Histone H2A variants H2AX and H2AZ. Curr. Opin. Genet. Dev. 2002, 12:162-169.
9. Kinner A., Wu W., Staudt C., Iliakis G. Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 2008, 36:5678-5694.
10. 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.
11. 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.
12. McManus K.J., Hendzel M.J. ATM-dependent DNA damage-independent mitotic phosphorylation of H2AX in normally growing mammalian cells. Mol. Biol. Cell 2005, 16:5013-5025.
13. Durocher D., Jackson S.P. DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?. Curr. Opin. Cell Biol. 2001, 13:225-231.
14. Celeste A., Fernandez-Capetillo O., Kruhlak M.J., Pilch D.R., Staudt D.W., Lee A., Bonner R.F., Bonner W.M., Nussenzweig A. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat. Cell Biol. 2003, 5:675-679.
15. Bhogal N., Jalali F., Bristow R.G. Microscopic imaging of DNA repair foci in irradiated normal tissues. Int. J. Radiat. Biol. 2009, 85:732-746.
16. Nakamura A.J., Rao V.A., Pommier Y., Bonner W.M. The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks. Cell Cycle 2010, 9:389-397.
17. Paull T.T., Rogakou E.P., Yamazaki V., Kirchgessner C.U., Gellert M., Bonner W.M. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr. Biol. 2000, 10:886-895.
18. 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 (Amst.) 2010, 9:1273-1282.
19. Lou Z., Minter-Dykhouse K., Franco S., Gostissa M., Rivera M.A., Celeste A., Manis J.P., van Deursen J., Nussenzweig A., Paull T.T., Alt F.W., Chen J. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 2006, 21:187-200.
20. Kobayashi J. Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain. J. Radiat. Res. 2004, 45:473-478.
21. Anderson L., Henderson C., Adachi Y. Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Mol. Cell. Biol. 2001, 21:1719-1729.
22. Furuta T., Takemura H., Liao Z.Y., Aune G.J., Redon C., Sedelnikova O.A., Pilch D.R., Rogakou E.P., Celeste A., Chen H.T., Nussenzweig A., Aladjem M.I., Bonner W.M., Pommier Y. Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J. Biol. Chem. 2003, 278:20303-20312.
23. 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.
24. Sedelnikova O.A., Rogakou E.P., Panyutin I.G., Bonner W.M. Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma-H2AX antibody. Radiat. Res. 2002, 158:486-492.
25. Rothkamm K., Lobrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low X-ray doses. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:5057-5062.
26. Doida Y., Okada S. Radiation-induced mitotic delay in cultured mammalian cells (L5178Y). Radiat. Res. 1969, 38:513-529.
27. Chowdhury D., Keogh M.C., Ishii H., Peterson C.L., Buratowski S., Lieberman J. Gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol. Cell 2005, 20:801-809.
28. Stiff T., O'Driscoll M., Rief N., Iwabuchi K., Lobrich M., Jeggo P.A. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 2004, 64:2390-2396.
29. Madigan J.P., Chotkowski H.L., Glaser R.L. DNA double-strand break-induced phosphorylation of Drosophila histone variant H2Av helps prevent radiation-induced apoptosis. Nucleic Acids Res. 2002, 30:3698-3705.
30. Roch-Lefevre S., Mandina T., Voisin P., Gaetan G., Mesa J.E., Valente M., Bonnesoeur P., Garcia O., Voisin P., Roy L. Quantification of gamma-H2AX foci in human lymphocytes: a method for biological dosimetry after ionizing radiation exposure. Radiat. Res. 2010, 174:185-194.
31. Olive P.L., Banath J.P. Phosphorylation of histone H2AX as a measure of radiosensitivity. Int. J. Radiat. Oncol. Biol. Phys. 2004, 58:331-335.
32. 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.
33. Moroni M., Maeda D., Whitnall M.H., Bonner W.M., Redon C.E. Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model. Int. J. Mol. Sci. 2013, 14:14119-14135.
34. Lobrich M., Rief N., Kuhne M., Heckmann M., Fleckenstein J., Rube C., Uder M. In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:8984-8989.
35. Fumagalli M., Rossiello F., Clerici M., Barozzi S., Cittaro D., Kaplunov J.M., Bucci G., Dobreva M., Matti V., Beausejour C.M., Herbig U., Longhese M.P., d'Adda di Fagagna F. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 2012, 14:355-365.
36. Hewitt G., Jurk D., Marques F.D., Correia-Melo C., Hardy T., Gackowska A., Anderson R., Taschuk M., Mann J., Passos J.F. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat. Commun. 2012, 3:708.
37. Torudd J., Protopopova M., Sarimov R., Nygren J., Eriksson S., Markova E., Chovanec M., Selivanova G., Belyaev I.Y. Dose-response for radiation-induced apoptosis, residual 53BP1 foci and DNA-loop relaxation in human lymphocytes. Int. J. Radiat. Biol. 2005, 81:125-138.
38. Bonner W.M., Redon C.E., Dickey J.S., Nakamura A.J., Sedelnikova O.A., Solier S., Pommier Y. GammaH2AX and cancer. Nat. Rev. Cancer 2008, 8:957-967.
39. Myung N.H., Zhu X., Kruman I.I., Castellani R.J., Petersen R.B., Siedlak S.L., Perry G., Smith M.A., Lee H.G. Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes. Age (Dordr.) 2008, 30:209-215.
40. Sedelnikova O.A., Horikawa I., Redon C., Nakamura A., Zimonjic D.B., Popescu N.C., Bonner W.M. Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell 2008, 7:89-100.
41. Schurman S.H., Dunn C.A., Greaves R., Yu B., Ferrucci L., Croteau D.L., Seidman M.M., Bohr V.A. Age-related disease association of endogenous gamma-H2AX foci in mononuclear cells derived from leukapheresis. PLoS ONE 2012, 7:e45728.
42. Pilch D.R., Redon C., Sedelnikova O.A., Bonner W.M. Two-dimensional gel analysis of histones and other H2AX-related methods. Methods Enzymol. 2004, 375:76-88.
43. Nakamura A., Sedelnikova O.A., Redon C., Pilch D.R., Sinogeeva N.I., Shroff R., Lichten M., Bonner W.M. Techniques for gamma-H2AX detection. Methods Enzymol. 2006, 409:236-250.
44. Hamasaki K., Imai K., Nakachi K., Takahashi N., Kodama Y., Kusunoki Y. Short-term culture and gammaH2AX flow cytometry determine differences in individual radiosensitivity in human peripheral T lymphocytes. Environ. Mol. Mutagen. 2007, 48:38-47.
45. Lassmann M., Hanscheid H., Gassen D., Biko J., Meineke V., Reiners C., Scherthan H. In vivo formation of gamma-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer. J. Nucl. Med. 2010, 51:1318-1325.
46. Bouquet F., Muller C., Salles B. The loss of gammaH2AX signal is a marker of DNA double strand breaks repair only at low levels of DNA damage. Cell Cycle 2006, 5:1116-1122.
47. Taneja N., Davis M., Choy J.S., Beckett M.A., Singh R., Kron S.J., Weichselbaum R.R. Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy. J. Biol. Chem. 2004, 279:2273-2280.
48. Siddiqui M.S., Francois M., Fenech M.F., Leifert W.R. gammaH2AX responses in human buccal cells exposed to ionizing radiation. Cytometry A 2014, 87:296-308.
49. Redon C.E., Dickey J.S., Bonner W.M., Sedelnikova O.A. Gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in human peripheral blood lymphocytes and artificial skin. Adv. Space Res. 2009, 43:1171-1178.
50. Willitzki A., Lorenz S., Hiemann R., Guttek K., Goihl A., Hartig R., Conrad K., Feist E., Sack U., Schierack P., Heiserich L., Eberle C., Peters V., Roggenbuck D., Reinhold D. Fully automated analysis of chemically induced gammaH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence. Cytometry A 2013, 83:1017-1026.
51. Runge R., Hiemann R., Wendisch M., Kasten-Pisula U., Storch K., Zophel K., Fritz C., Roggenbuck D., Wunderlich G., Conrad K., Kotzerke J. Fully automated interpretation of ionizing radiation-induced gammaH2AX foci by the novel pattern recognition system AKLIDES(R). Int. J. Radiat. Biol. 2012, 88:439-447.
52. Brzozowska K., Pinkawa M., Eble M.J., Muller W.U., Wojcik A., Kriehuber R., Schmitz S. In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy. Int. J. Radiat. Biol. 2012, 88:405-413.
53. Zhao H., Albino A.P., Jorgensen E., Traganos F., Darzynkiewicz Z. DNA damage response induced by tobacco smoke in normal human bronchial epithelial and A549 pulmonary adenocarcinoma cells assessed by laser scanning cytometry. Cytometry A 2009, 75:840-847.
54. Tanaka T., Huang X., Halicka H.D., Zhao H., Traganos F., Albino A.P., Dai W., Darzynkiewicz Z. Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents. Cytometry A 2007, 71:648-661.
55. Riballo E., Kuhne M., Rief N., Doherty A., Smith G.C., Recio M.J., Reis C., Dahm K., Fricke A., Krempler A., Parker A.R., Jackson S.P., Gennery A., Jeggo P.A., Lobrich M. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol. Cell 2004, 16:715-724.
56. Lobrich M., Shibata A., Beucher A., Fisher A., Ensminger M., Goodarzi A.A., Barton O., Jeggo P.A. gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle 2010, 9:662-669.
57. Goodhead D.T. Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. Int. J. Radiat. Biol. 1994, 65:7-17.
58. Sharma P.M., Ponnaiya B., Taveras M., Shuryak I., Turner H., Brenner D.J. High throughput measurement of gammaH2AX DSB repair kinetics in a healthy human population. PLOS ONE 2015, 10:e0121083.
59. Kodym R., Horth E. Determination of radiation-induced DNA strand breaks in individual cells by non-radioactive labelling of 3' OH ends. Int. J. Radiat. Biol. 1995, 68:133-139.
60. Nunez M.I., Villalobos M., Olea N., Valenzuela M.T., Pedraza V., McMillan T.J., Ruiz de Almodovar J.M. Radiation-induced DNA double-strand break rejoining in human tumour cells. Br. J. Cancer 1995, 71:311-316.
61. MacPhail S.H., Banath J.P., Yu Y., Chu E., Olive P.L. Cell cycle-dependent expression of phosphorylated histone H2AX: reduced expression in unirradiated but not X-irradiated G1-phase cells. Radiat. Res. 2003, 159:759-767.
62. Ward J.F. DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Prog. Nucleic Acid Res. Mol. Biol. 1988, 35:95-125.
63. Ward J.F. The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int. J. Radiat. Biol. 1990, 57:1141-1150.
64. Banath J.P., Klokov D., MacPhail S.H., Banuelos C.A., Olive P.L. Residual gammaH2AX foci as an indication of lethal DNA lesions. BMC Cancer 2010, 10:4.
65. Bhogal N., Kaspler P., Jalali F., Hyrien O., Chen R., Hill R.P., Bristow R.G. Late residual gamma-H2AX foci in murine skin are dose responsive and predict radiosensitivity in vivo. Radiat. Res. 2010, 173:1-9.
66. Djuzenova C.S., Elsner I., Katzer A., Worschech E., Distel L.V., Flentje M., Polat B. Radiosensitivity in breast cancer assessed by the histone gamma-H2AX and 53BP1 foci. Radiat. Oncol. 2013, 8:98.
67. Jeggo P.A., Geuting V., Lobrich M. The role of homologous recombination in radiation-induced double-strand break repair. Radiother. Oncol. 2011, 101:7-12.
68. MacPhail S.H., Banath J.P., Yu T.Y., Chu E.H., Lambur H., Olive P.L. Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X-rays. Int. J. Radiat. Biol. 2003, 79:351-358.
69. Dikomey E., Dahm-Daphi J., Brammer I., Martensen R., Kaina B. Correlation between cellular radiosensitivity and non-repaired double-strand breaks studied in nine mammalian cell lines. Int. J. Radiat. Biol. 1998, 73:269-278.
70. Redon C.E., Nakamura A.J., Gouliaeva K., Rahman A., Blakely W.F., Bonner W.M. The use of gamma-H2AX as a biodosimeter for total-body radiation exposure in non-human primates. PLoS ONE 2010, 5:e15544.
71. Qvarnstrom O.F., Simonsson M., Johansson K.A., Nyman J., Turesson I. DNA double strand break quantification in skin biopsies. Radiother. Oncol. 2004, 72:311-317.
72. Paris L., Cordelli E., Eleuteri P., Grollino M.G., Pasquali E., Ranaldi R., Meschini R., Pacchierotti F. Kinetics of gamma-H2AX induction and removal in bone marrow and testicular cells of mice after X-ray irradiation. Mutagenesis 2011, 26:563-572.
73. Markova E., Schultz N., Belyaev I.Y. Kinetics and dose-response of residual 53BP1/gamma-H2AX foci: co-localization, relationship with DSB repair and clonogenic survival. Int. J. Radiat. Biol. 2007, 83:319-329.
74. Bracalente C., Ibanez I.L., Molinari B., Palmieri M., Kreiner A., Valda A., Davidson J., Duran H. Induction and persistence of large gammaH2AX foci by high linear energy transfer radiation in DNA-dependent protein kinase-deficient cells. Int. J. Radiat. Oncol. Biol. Phys. 2013, 87:785-794.
75. Zalenskaya I.A., Bradbury E.M., Zalensky A.O. Chromatin structure of telomere domain in human sperm. Biochem. Biophys. Res. Commun. 2000, 279:213-218.
76. Ismail I.H., Wadhra T.I., Hammarsten O. An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans. Nucleic Acids Res. 2007, 35:e36.
77. Sak A., Grehl S., Erichsen P., Engelhard M., Grannass A., Levegrun S., Pottgen C., Groneberg M., Stuschke M. Gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment. Int. J. Radiat. Biol. 2007, 83:639-652.
78. Kasten-Pisula U., Windhorst S., Dahm-Daphi J., Mayr G., Dikomey E. Radiosensitization of tumour cell lines by the polyphenol gossypol results from depressed double-strand break repair and not from enhanced apoptosis. Radiother. Oncol. 2007, 83:296-303.
79. Ivashkevich A., Redon C.E., Nakamura A.J., Martin R.F., Martin O.A. Use of the gamma-H2AX assay to monitor DNA damage and repair in translational cancer research. Cancer Lett. 2012, 327:123-133.
80. Andrievski A., Wilkins R.C. The response of gamma-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures. Int. J. Radiat. Biol. 2009, 85:369-376.
81. Turesson I., Nyman J., Holmberg E., Oden A. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int. J. Radiat. Oncol. Biol. Phys. 1996, 36:1065-1075.
82. Fleckenstein J., Kuhne M., Seegmuller K., Derschang S., Melchior P., Graber S., Fricke A., Rube C.E., Rube C. The impact of individual in vivo repair of DNA double-strand breaks on oral mucositis in adjuvant radiotherapy of head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 2011, 81:1465-1472.
83. Bourton E.C., Plowman P.N., Smith D., Arlett C.F., Parris C.N. Prolonged expression of the gamma-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment. Int. J. Cancer 2011, 129:2928-2934.
84. Werbrouck J., De Ruyck K., Beels L., Vral A., Van Eijkeren M., De Neve W., Thierens H. Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the gamma-H2AX foci assay and association with chromosomal radiosensitivity. Oncol. Rep. 2010, 23:571-578.
85. Tucker S.L., Geara F.B., Peters L.J., Brock W.A. How much could the radiotherapy dose be altered for individual patients based on a predictive assay of normal-tissue radiosensitivity?. Radiother. Oncol. 1996, 38:103-113.
86. Cox J.D., Stetz J., Pajak T.F. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int. J. Radiat. Oncol. Biol. Phys. 1995, 31:1341-1346.
87. Rube C.E., Fricke A., Schneider R., Simon K., Kuhne M., Fleckenstein J., Graber S., Graf N., Rube C. DNA repair alterations in children with pediatric malignancies: novel opportunities to identify patients at risk for high-grade toxicities. Int. J. Radiat. Oncol. Biol. Phys. 2010, 78:359-369.
88. Chua M.L., Somaiah N., A'Hern R., Davies S., Gothard L., Yarnold J., Rothkamm K. Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. Radiother. Oncol. 2011, 99:362-366.
89. Goutham H.V., Mumbrekar K.D., Vadhiraja B.M., Fernandes D.J., Sharan K., Kanive Parashiva G., Kapaettu S., Bola S.R., Sadashiva DNA double-strand break analysis by gamma-H2AX foci: a useful method for determining the overreactors to radiation-induced acute reactions among head-and-neck cancer patients. Int. J. Radiat. Oncol. Biol. Phys. 2012, 84:e607-e612.
90. Morini J., Babini G., Mariotti L., Baiocco G., Nacci L., Maccario C., Rossler U., Minelli A., Savio M., Gomolka M., Kulka U., Ottolenghi A., Danesino C. Radiosensitivity in lymphoblastoid cell lines derived from Shwachman-Diamond syndrome patients. Radiat. Prot. Dosimetry 2015, 10.1093/rpd/ncv152.
91. Porcedda P., Turinetto V., Lantelme E., Fontanella E., Chrzanowska K., Ragona R., De Marchi M., Delia D., Giachino C. Impaired elimination of DNA double-strand break-containing lymphocytes in ataxia telangiectasia and Nijmegen breakage syndrome. DNA Repair (Amst.) 2006, 5:904-913.
92. Doai M., Watanabe N., Takahashi T., Taniguchi M., Tonami H., Iwabuchi K., Kayano D., Fukuoka M., Kinuya S. Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using gamma-H2AX foci of DNA damage in lymphocytes. Ann. Nucl. Med. 2013, 27:233-238.
93. May M.S., Brand M., Wuest W., Anders K., Kuwert T., Prante O., Schmidt D., Maschauer S., Semelka R.C., Uder M., Kuefner M.A. Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing (1)(8)F-FDG PET/CT examinations. Eur. J. Nucl. Med. Mol. Imaging 2012, 39:1712-1719.
94. Denoyer D., Lobachevsky P., Jackson P., Thompson M., Martin O.A., Hicks R.J. Analysis of 177Lu-DOTA-octreotate therapy-induced DNA damage in peripheral blood lymphocytes of patients with neuroendocrine tumors. J. Nucl. Med. 2015, 56:505-511.
95. Geisel D., Heverhagen J.T., Kalinowski M., Wagner H.J. DNA double-strand breaks after percutaneous transluminal angioplasty. Radiology 2008, 248:852-859.
96. Markova E., Torudd J., Belyaev I. Long time persistence of residual 53BP1/gamma-H2AX foci in human lymphocytes in relationship to apoptosis, chromatin condensation and biological dosimetry. Int. J. Radiat. Biol. 2011, 87:736-745.
97. Rodier F., Coppe J.P., Patil C.K., Hoeijmakers W.A., Munoz D.P., Raza S.R., Freund A., Campeau E., Davalos A.R., Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 2009, 11:973-979.
98. Baynton K., Otterlei M., Bjoras M., von Kobbe C., Bohr V.A., Seeberg E. WRN interacts physically and functionally with the recombination mediator protein RAD52. J. Biol. Chem. 2003, 278:36476-36486.
99. Huang S., Lee L., Hanson N.B., Lenaerts C., Hoehn H., Poot M., Rubin C.D., Chen D.F., Yang C.C., Juch H., Dorn T., Spiegel R., Oral E.A., Abid M., Battisti C., Lucci-Cordisco E., Neri G., Steed E.H., Kidd A., Isley W., Showalter D., Vittone J.L., Konstantinow A., Ring J., Meyer P., Wenger S.L., von Herbay A., Wollina U., Schuelke M., Huizenga C.R., Leistritz D.F., Martin G.M., Mian I.S., Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum. Mutat. 2006, 27:558-567.
100. Lan L., Nakajima S., Komatsu K., Nussenzweig A., Shimamoto A., Oshima J., Yasui A. Accumulation of Werner protein at DNA double-strand breaks in human cells. J. Cell Sci. 2005, 118:4153-4162.
101. Zecevic A., Menard H., Gurel V., Hagan E., DeCaro R., Zhitkovich A. WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle 2009, 8:2769-2778.
102. Cantor S.B., Brosh R.M. What is wrong with Fanconi anemia cells?. Cell Cycle 2014, 13:3823-3827.
103. Leskovac A., Vujic D., Guc-Scekic M., Petrovic S., Joksic I., Slijepcevic P., Joksic G. Fanconi anemia is characterized by delayed repair kinetics of DNA double-strand breaks. Tohoku J. Exp. Med. 2010, 221:69-76.
104. Gonzalez J.E., Roch-Lefevre S.H., Mandina T., Garcia O., Roy L. Induction of gamma-H2AX foci in human exfoliated buccal cells after in vitro exposure to ionising radiation. Int. J. Radiat. Biol. 2010, 86:752-759.
105. Filion T.M., Qiao M., Ghule P.N., Mandeville M., van Wijnen A.J., Stein J.L., Lian J.B., Altieri D.C., Stein G.S. Survival responses of human embryonic stem cells to DNA damage. J. Cell. Physiol. 2009, 220:586-592.
106. Rube C.E., Fricke A., Widmann T.A., Furst T., Madry H., Pfreundschuh M., Rube C. Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS ONE 2011, 6:e17487.
107. Klokov D., MacPhail S.M., Banath J.P., Byrne J.P., Olive P.L. Phosphorylated histone H2AX in relation to cell survival in tumor cells and xenografts exposed to single and fractionated doses of X-rays. Radiother. Oncol. 2006, 80:223-229.
108. Smogorzewska A., Karlseder J., Holtgreve-Grez H., Jauch A., de Lange T. DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr. Biol. 2002, 12:1635-1644.
109. Menegakis A., Yaromina A., Eicheler W., Dorfler A., Beuthien-Baumann B., Thames H.D., Baumann M., Krause M. Prediction of clonogenic cell survival curves based on the number of residual DNA double strand breaks measured by gammaH2AX staining. Int. J. Radiat. Biol. 2009, 85:1032-1041.
110. Ahmed E.A., van der Vaart A., Barten A., Kal H.B., Chen J., Lou Z., Minter-Dykhouse K., Bartkova J., Bartek J., de Boer P., de Rooij D.G. Differences in DNA double strand breaks repair in male germ cell types: lessons learned from a differential expression of Mdc1 and 53BP1. DNA Repair (Amst.) 2007, 6:1243-1254.
111. Andratschke N., Blau T., Schill S., Nieder C. Late residual gamma-H2AX foci in murine spinal cord might facilitate development of response-modifying strategies: a research hypothesis. Anticancer Res. 2011, 31:561-564.
112. Meyn R.E., Jenkins W.T. Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo. Cancer Res. 1983, 43:5668-5673.
113. Yoshida K., Yoshida S.H., Shimoda C., Morita T. Expression and radiation-induced phosphorylation of histone H2AX in mammalian cells. J. Radiat. Res. 2003, 44:47-51.
114. Gavrilov B., Vezhenkova I., Firsanov D., Solovjeva L., Svetlova M., Mikhailov V., Tomilin N. Slow elimination of phosphorylated histone gamma-H2AX from DNA of terminally differentiated mouse heart cells in situ. Biochem. Biophys. Res. Commun. 2006, 347:1048-1052.
115. Hudson D., Kovalchuk I., Koturbash I., Kolb B., Martin O.A., Kovalchuk O. Induction and persistence of radiation-induced DNA damage is more pronounced in young animals than in old animals. Aging (Albany, NY) 2011, 3:609-620.
116. Rube C.E., Dong X., Kuhne M., Fricke A., Kaestner L., Lipp P., Rube C. DNA double-strand break rejoining in complex normal tissues. Int. J. Radiat. Oncol. Biol. Phys. 2008, 72:1180-1187.
117. Grudzenski S., Raths A., Conrad S., Rube C.E., Lobrich M. Inducible response required for repair of low-dose radiation damage in human fibroblasts. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:14205-14210.
118. Ahmed E.A., Agay D., Schrock G., Drouet M., Meineke V., Scherthan H. Persistent DNA damage after high dose in vivo gamma exposure of minipig skin. PLoS ONE 2012, 7:e39521.
119. Siddiqui M.S., Filomeni E., Francois M., Collins S.R., Cooper T., Glatz R.V., Taylor P.W., Fenech M., Leifert W.R. Exposure of insect cells to ionising radiation in vivo induces persistent phosphorylation of a H2AX homologue (H2AvB). Mutagenesis 2013, 28:531-541.
120. Firsanov D., Vasilishina A., Kropotov A., Mikhailov V. Dynamics of gammaH2AX formation and elimination in mammalian cells after X-irradiation. Biochimie 2012, 94:2416-2422.
121. McEachern M.J., Krauskopf A., Blackburn E.H. Telomeres and their control. Annu. Rev. Genet. 2000, 34:331-358.
122. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005, 19:2100-2110.
123. Bae N.S., Baumann P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol. Cell 2007, 26:323-334.
124. Passos J.F., Nelson G., Wang C., Richter T., Simillion C., Proctor C.J., Miwa S., Olijslagers S., Hallinan J., Wipat A., Saretzki G., Rudolph K.L., Kirkwood T.B., von Zglinicki T. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol. Syst. Biol. 2010, 6:347.
125. d'Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat. Rev. Cancer 2008, 8:512-522.
126. Campisi J., d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 2007, 8:729-740.
127. Dimri G.P., Lee X., Basile G., Acosta M., Scott G., Roskelley C., Medrano E.E., Linskens M., Rubelj I., Pereira-Smith O. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U. S. A. 1995, 92:9363-9367.
128. 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.
129. Aubert G., Lansdorp P.M. Telomeres and aging. Physiol. Rev. 2008, 88:557-579.
130. Lopez-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell 2013, 153:1194-1217.
131. Sinclair D.A., Oberdoerffer P. The ageing epigenome: damaged beyond repair?. Ageing Res. Rev. 2009, 8:189-198.
132. Gedik C.M., Grant G., Morrice P.C., Wood S.G., Collins A.R. Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats. Eur. J. Nutr. 2005, 44:263-272.
133. Harley C.B., Futcher A.B., Greider C.W. Telomeres shorten during ageing of human fibroblasts. Nature 1990, 345:458-460.
134. Hastie N.D., Dempster M., Dunlop M.G., Thompson A.M., Green D.K., Allshire R.C. Telomere reduction in human colorectal carcinoma and with ageing. Nature 1990, 346:866-868.
135. Campisi J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 2013, 75:685-705.
136. d'Adda di Fagagna F., Reaper P.M., Clay-Farrace L., Fiegler H., Carr P., Von Zglinicki T., Saretzki G., Carter N.P., Jackson S.P. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003, 426:194-198.
137. Stein G.H., Drullinger L.F., Robetorye R.S., Pereira-Smith O.M., Smith J.R. Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation. Proc. Natl. Acad. Sci. U. S. A. 1991, 88:11012-11016.
138. Baker D.J., Wijshake T., Tchkonia T., LeBrasseur N.K., Childs B.G., van de Sluis B., Kirkland J.L., van Deursen J.M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479:232-236.
139. Wang C., Jurk D., Maddick M., Nelson G., Martin-Ruiz C., von Zglinicki T. DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 2009, 8:311-323.
140. Sikora E., Arendt T., Bennett M., Narita M. Impact of cellular senescence signature on ageing research. Ageing Res. Rev. 2011, 10:146-152.
141. Campisi J., Andersen J.K., Kapahi P., Melov S. Cellular senescence: a link between cancer and age-related degenerative disease?. Semin. Cancer Biol. 2011, 21:354-359.
142. Freund A., Orjalo A.V., Desprez P.Y., Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 2010, 16:238-246.
143. Chung H.Y., Cesari M., Anton S., Marzetti E., Giovannini S., Seo A.Y., Carter C., Yu B.P., Leeuwenburgh C. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res. Rev. 2009, 8:18-30.
144. Franceschi C. Inflammaging as a major characteristic of old people: can it be prevented or cured?. Nutr. Rev. 2007, 65:S173-S176.
145. Garm C., Moreno-Villanueva M., Burkle A., Petersen I., Bohr V.A., Christensen K., Stevnsner T. Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells. Aging Cell 2013, 12:58-66.
146. Endt H., Sprung C.N., Keller U., Gaipl U., Fietkau R., Distel L.V. Detailed analysis of DNA repair and senescence marker kinetics over the life span of a human fibroblast cell line. J. Gerontol. A: Biol. Sci. Med. Sci. 2011, 66:367-375.
147. Herbig U., Ferreira M., Condel L., Carey D., Sedivy J.M. Cellular senescence in aging primates. Science 2006, 311:1257.
148. Gorbunova V., Seluanov A. Making ends meet in old age: DSB repair and aging. Mech. Ageing Dev. 2005, 126:621-628.
149. Scarpato R., Verola C., Fabiani B., Bianchi V., Saggese G., Federico G. Nuclear damage in peripheral lymphocytes of obese and overweight Italian children as evaluated by the gamma-H2AX focus assay and micronucleus test. FASEB J. 2011, 25:685-693.
150. Giovannini C., Piaggi S., Federico G., Scarpato R. High levels of gamma-H2AX foci and cell membrane oxidation in adolescents with type 1 diabetes. Mutat. Res. 2014, 770:128-135.
151. Liu Y., Rusinol A., Sinensky M., Wang Y., Zou Y. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J. Cell Sci. 2006, 119:4644-4649.
152. Hoze N., Ruault M., Amoruso C., Taddei A., Holcman D. Spatial telomere organization and clustering in yeast Saccharomyces cerevisiae nucleus is generated by a random dynamics of aggregation-dissociation. Mol. Biol. Cell 2013, 24(1791-800):S1-S10.
153. Moquet J., Barnard S., Rothkamm K. Gamma-H2AX biodosimetry for use in large scale radiation incidents: comparison of a rapid '96 well lyse/fix' protocol with a routine method. PeerJ 2014, 2:e282.
154. Turner H.C., Brenner D.J., Chen Y., Bertucci A., Zhang J., Wang H., Lyulko O.V., Xu Y., Shuryak I., Schaefer J., Simaan N., Randers-Pehrson G., Yao Y.L., Amundson S.A., Garty G. Adapting the gamma-H2AX assay for automated processing in human lymphocytes: 1. Technological aspects. Radiat. Res. 2011, 175:282-290.
155. Garty G., Chen Y., Salerno A., Turner H., Zhang J., Lyulko O., Bertucci A., Xu Y., Wang H., Simaan N., Randers-Pehrson G., Yao Y.L., Amundson S.A., Brenner D.J. The RABIT: a rapid automated biodosimetry tool for radiological triage. Health Phys. 2010, 98:209-217.
156. Bekker-Jensen S., Lukas C., Kitagawa R., Melander F., Kastan M.B., Bartek J., Lukas J. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J. Cell Biol. 2006, 173:195-206.
157. Mari P.O., Florea B.I., Persengiev S.P., Verkaik N.S., Bruggenwirth H.T., Modesti M., Giglia-Mari G., Bezstarosti K., Demmers J.A., Luider T.M., Houtsmuller A.B., van Gent D.C. Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:18597-18602.
158. Li W., Li F., Huang Q., Shen J., Wolf F., He Y., Liu X., Hu Y.A., Bedford J.S., Li C.Y. Quantitative, noninvasive imaging of radiation-induced DNA double-strand breaks in vivo. Cancer Res. 2011, 71:4130-4137.
159. Cornelissen B., Kersemans V., Darbar S., Thompson J., Shah K., Sleeth K., Hill M.A., Vallis K.A. Imaging DNA damage in vivo using gammaH2AX-targeted immunoconjugates. Cancer Res. 2011, 71:4539-4549.
160. Leonard A., Rueff J., Gerber G.B., Leonard E.D. Usefulness and limits of biological dosimetry based on cytogenetic methods. Radiat. Prot. Dosimetry 2005, 115:448-454.
161. Kleinerman R.A., Romanyukha A.A., Schauer D.A., Tucker J.D. Retrospective assessment of radiation exposure using biological dosimetry: chromosome painting, electron paramagnetic resonance and the glycophorin a mutation assay. Radiat Res. 2006, 166:287-302.
162. Pinto M.M., Santos N.F., Amaral A. Current status of biodosimetry based on standard cytogenetic methods. Radiat. Environ. Biophys. 2010, 49:567-581.
163. Banath J.P., Macphail S.H., Olive P.L. Radiation sensitivity, H2AX phosphorylation, and kinetics of repair of DNA strand breaks in irradiated cervical cancer cell lines. Cancer Res. 2004, 64:7144-7149.
164. Mohapatra S., Kawahara M., Khan I.S., Yannone S.M., Povirk L.F. Restoration of G1 chemo/radioresistance and double-strand-break repair proficiency by wild-type but not endonuclease-deficient artemis. Nucleic Acids Res. 2011, 39:6500-6510.
165. Zhao J., Guo Z., Zhang H., Wang Z., Song L., Ma J., Pei S., Wang C. The potential value of the neutral comet assay and gammaH2AX foci assay in assessing the radiosensitivity of carbon beam in human tumor cell lines. Radiol. Oncol. 2013, 47:247-257.
166. Balcer-Kubiczek E.K., Attarpour M., Edelman M.J. The synergistic effect of dimethylamino benzoylphenylurea (NSC #639829) and X-irradiation on human lung carcinoma cell lines. Cancer Chemother. Pharmacol. 2007, 59:781-787.
167. Baschnagel A., Russo A., Burgan W.E., Carter D., Beam K., Palmieri D., Steeg P.S., Tofilon P., Camphausen K. Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts. Mol. Cancer Ther. 2009, 8:1589-1595.
168. Huerta S., Gao X., Livingston E.H., Kapur P., Sun H., Anthony T. In vitro and in vivo radiosensitization of colorectal cancer HT-29 cells by the smac mimetic JP-1201. Surgery 2010, 148:346-353.
169. Choudhuri R., Degraff W., Gamson J., Mitchell J.B., Cook J.A. Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines. Front. Oncol. 2011, 1:19.
170. Wang L., Raju U., Milas L., Molkentine D., Zhang Z., Yang P., Cohen L., Meng Z., Liao Z. Huachansu, containing cardiac glycosides, enhances radiosensitivity of human lung cancer cells. Anticancer Res. 2011, 31:2141-2148.
171. Wang H., Wang M., Wang H., Bocker W., Iliakis G. Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors. J. Cell. Physiol. 2005, 202:492-502.
172. Fu S., Yang Y., Das T.K., Yen Y., Zhou B.S., Zhou M.M., Ohlmeyer M., Ko E.C., Cagan R., Rosenstein B.S., Chen S.H., Kao J. Gamma-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers. PLoS ONE 2012, 7:e38465.
173. Kuhne M., Riballo E., Rief N., Rothkamm K., Jeggo P.A., Lobrich M. A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res. 2004, 64:500-508.
174. Kim Y.B., Jeung H.C., Jeong I., Lee K., Rha S.Y., Chung H.C., Kim G.E. Mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer. J. Radiat. Res. 2013, 54:52-60.
175. Minieri V., Saviozzi S., Gambarotta G., Lo Iacono M., Accomasso L., Cibrario Rocchietti E., Gallina C., Turinetto V., Giachino C. Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells. J. Cell. Mol. Med. 2015, 19:734-743.
176. McKenna E., Traganos F., Zhao H., Darzynkiewicz Z. Persistent DNA damage caused by low levels of mitomycin C induces irreversible cell senescence. Cell Cycle 2012, 11:3132-3140.
177. Wei D., Parsels L.A., Karnak D., Davis M.A., Parsels J.D., Marsh A.C., Zhao L., Maybaum J., Lawrence T.S., Sun Y., Morgan M.A. Inhibition of protein phosphatase 2A radiosensitizes pancreatic cancers by modulating CDC25C/CDK1 and homologous recombination repair. Clin. Cancer Res. 2013, 19:4422-4432.
178. Wang J., Liu Q., Yang Q. Radiosensitization effects of berberine on human breast cancer cells. Int. J. Mol. Med. 2012, 30:1166-1172.
179. Fahrer J., Huelsenbeck J., Jaurich H., Dorsam B., Frisan T., Eich M., Roos W.P., Kaina B., Fritz G. Cytolethal distending toxin (CDT) is a radiomimetic agent and induces persistent levels of DNA double-strand breaks in human fibroblasts. DNA Repair (Amst.) 2014, 18:31-43.
180. Chiu S.J., Chao J.I., Lee Y.J., Hsu T.S. Regulation of gamma-H2AX and securin contribute to apoptosis by oxaliplatin via a p38 mitogen-activated protein kinase-dependent pathway in human colorectal cancer cells. Toxicol. Lett. 2008, 179:63-70.
181. Morgan M.A., Parsels L.A., Zhao L., Parsels J.D., Davis M.A., Hassan M.C., Arumugarajah S., Hylander-Gans L., Morosini D., Simeone D.M., Canman C.E., Normolle D.P., Zabludoff S.D., Maybaum J., Lawrence T.S. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 2010, 70:4972-4981.
182. Wu J., Clingen P.H., Spanswick V.J., Mellinas-Gomez M., Meyer T., Puzanov I., Jodrell D., Hochhauser D., Hartley J.A. Gamma-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000). Clin. Cancer Res. 2013, 19:721-730.
183. Ladd B., O'Konek J.J., Ostruszka L.J., Shewach D.S. Unrepairable DNA double-strand breaks initiate cytotoxicity with HSV-TK/ganciclovir. Cancer Gene Ther. 2011, 18:751-759.
184. Alessio N., Del Gaudio S., Capasso S., Di Bernardo G., Cappabianca S., Cipollaro M., Peluso G., Galderisi U. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget 2015, 6:8155-8166.
185. Groesser T., Chang H., Fontenay G., Chen J., Costes S.V., Helen Barcellos-Hoff M., Parvin B., Rydberg B. Persistence of gamma-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to gamma-rays or iron ions. Int. J. Radiat. Biol. 2011, 87:696-710.
186. Suzuki M., Suzuki K., Kodama S., Watanabe M. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest. Biochem. Biophys. Res. Commun. 2006, 340:145-150.