Abstract
PML nuclear bodies (PML NBs) respond to many cellular stresses including viral infection, heat shock, arsenic and oncogenes and have been implicated in the regulation of p53-dependent replicative senescence and apoptosis. Recently, the hMre11/Rad50/NBS1 repair complex, involved in Double Strand Breaks (DSBs) repair, was found to colocalize within PML NBs, suggesting a role for these nuclear sub-domains in the DNA repair signalling pathway. We report here that in normal human fibroblasts, after ionizing radiation (IR), the PML NBs are modified and recognize sites of DNA breaks (ssDNA breaks and DSBs). Eight to 12 h after radiation PML NBs associate with hMre11 Ionizing Radiation-Induced Foci (IRIF), and subsequently with p53 within discrete foci. The PML, hMre11 and p53 colocalizing structures mark sites of DSBs as identified by immunolocalization with anti phosphorylated histone γ-H2AX. Furthermore, we demonstrate that ionizing radiation induces the stable association of p53 with hMre11 and PML. These results suggest that the PML NBs are involved in the recognition and/or processing of DNA breaks and possibly in the recruitment of proteins (p53 and hMre11) required for both checkpoint and DNA-repair responses.
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References
Ahn JH, Hayward GS . 2000 Virology 274: 39–55
Andre C, Guillemin MC, Zhu J, Koken MH, Quignon F, Herve L, Chelbi-Alix MK, Dhumeaux D, Wang ZY, Degos L, Chen Z, de The H . 1996 Exp. Cell Res. 229: 253–260
Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J . 2001 J. Cell. Biol. 16: 367–380
Boisvert FM, Kruhlak MJ, Box AK, Hendzel MJ, Bazett-Jones DP . 2001 J. Cell. Biol. 152: 1099–1106
Borrow J, Goddard AD, Sheer D, Solomon E . 1990 Science 249: 1577–1580
Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM . 1997 Proc. Natl. Acad. Sci. USA 94: 2551–2556
Buchhop S, Gibson MK, Wang XW, Wagner P, Sturzbecher HW, Harris CC . 1997 Nucleic Acids Res. 25: 3868–3874
Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates III JR, Hays L, Morgan WF, Petrini JH . 1998 Cell 93: 477–486
Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN . 1999 Oncogene 18: 263–268
Chang KS, Fan YH, Andreeff M, Liu J, Mu ZM . 1995 Blood 85: 3646–3653
de The H, Chomienne C, Lanotte M, Degos L, Dejean A . 1990 Nature 347: 558–561
Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH . 1996 Mol. Cell. Biol. 16: 4832–4841
Everett RD, Earnshaw WC, Pluta AF, Sternsdorf T, Ainsztein AM, Carmena M, Ruchaud S, Hsu WL, Orr A . 1999 J. Cell. Sci. 112: 3443–3454
Everett RD, Freemont P, Saitoh H, Dasso M, Orr A, Kathoria M, Parkinson J . 1998 J. Virol. 72: 6581–6591
Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW . 2000 Genes Dev. 14: 2015–2027
Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G . 2000 EMBO J. 19: 6185–6195
Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Paolo Pandolfi P . 2000 Nat. Cell. Biol. 2: 730–736
Hwang BJ, Ford JM, Hanawalt PC, Chu G . 1999 Proc. Natl. Acad. Sci. USA 96: 424–428
Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss III JF, Maul GG . 1999 J. Cell. Biol. 147: 221–234
Kelly C, Van Driel R, Wilkinson GW . 1995 J. Gen. Virol. 76: 2887–2893
Khanna KK, Jackson SP . 2001 Nat. Genet. 27: 247–254
Ko LJ, Prives C . 1996 Genes Dev. 10: 1054–1072
Lombard DB, Guarente L . 2000 Cancer Res. 60: 2331–2334
Lozano G, Elledge SJ . 2000 Nature 404: 24–25
Maser RS, Monsen KJ, Nelms BE, Petrini JH . 1997 Mol. Cell. Biol. 17: 6087–6096
Maul GG, Yu E, Ishov AM, Epstein AL . 1995 J. Cell. Biochem. 59: 498–513
Mirzoeva OK, Petrini JH . 2001 Mol. Cell. Biol. 21: 281–288
Muller S, Miller Jr WH, Dejean A . 1998 Blood 92: 4308–4316
Mummenbrauer T, Janus F, Muller B, Wiesmuller L, Deppert W, Grosse F . 1996 Cell 85: 1089–1099
Offer H, Milyavsky M, Erez N, Matas D, Zurer I, Harris CC, Rotter V . 2001 Oncogene 5: 581–589
Paull TT, Gellert M . 1998 Mol. Cell. 1: 969–979
Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM . 2000 Curr. Biol. 10: 886–895
Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP, Pelicci PG . 2000 Nature 406: 207–210
Petrini JH . 1999 Am. J. Hum. Genet. 64: 1264–1269
Raderschall E, Golub EI, Haaf T . 1999 Proc. Natl. Acad. Sci. USA 96: 1921–1926
Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM . 1998 J. Biol. Chem. 273: 5858–5868
Rogakou EP, Boon C, Redon C, Bonner WM . 1999 J. Cell. Biol. 5: 905–916
Skalski V, Lin ZY, Choi BY, Brown KR . 2000 Oncogene 19: 3321–3329
Smith ML, Ford JM, Hollander MC, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC, Fornace Jr AJ . 2000 Mol. Cell. Biol. 20: 3705–3714
Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, Raams A, Byrd PJ, Petrini JH, Taylor AM . 1999 Cell 99: 577–587
Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y . 2000 Nature 404: 42–49
Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J . 2000 Genes Dev. 14: 927–939
Zhong S, Hu P, Ye TZ, Stan R, Ellis NA, Pandolfi PP . 1999 Oncogene 18: 7941–7947
Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP . 2000 J. Exp. Med. 191: 631–640
Zhou J, Ahn J, Wilson SH, Prives C . 2001 EMBO J. 20: 914–923
Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z, de The H . 1997 Proc. Natl. Acad. Sci. USA 94: 3978–3983
Acknowledgements
We thank Pietro Transidico for technical assistance in confocal analysis and the Service of Medical Physics of our Institute for technical help. This work was supported by grants from AIRC and the EC.
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Carbone, R., Pearson, M., Minucci, S. et al. PML NBs associate with the hMre11 complex and p53 at sites of irradiation induced DNA damage. Oncogene 21, 1633–1640 (2002). https://doi.org/10.1038/sj.onc.1205227
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DOI: https://doi.org/10.1038/sj.onc.1205227
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