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UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML

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Abstract

The promyelocytic leukemia protein (PML) is a nuclear phosphoprotein that localizes to distinct domains in the nucleus, described as PML nuclear bodies (PML-NBs). Recent findings indicate that PML regulates the p53 response to oncogenic signals. Here, we define a p53-dependent role for PML in response to DNA damage. We exposed cells to ultraviolet light (UV-C) and imaged the nuclear distribution of PML, p53, and the BLM helicase by confocal microscopy. After DNA damage, PML partially relocated out of the PML-NBs, and colocalized with BLM and p53 at sites of DNA repair. In addition, using the isogenic HCT116 cell lines (p53+/+ and −/−), we show that the redistribution of PML was dependent on functional p53. Western analysis revealed that the level of PML protein remained unaltered after UV-C treatment. These results are consistent with the hypothesis that PML, in conjunction with p53 and BLM, contributes to the cellular response to UV-C-induced DNA damage and its repair.

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References

  • Adamson AL and Kenney S . (2001). J. Virol., 75, 2388–2399.

  • Ahn JH and Hayward GS . (2000). Virology, 274, 39–55.

  • Auerbach AD and Verlander PC . (1997). Curr. Opin. Pediatr., 9, 600–616.

  • Bischof O, Kim SH, Irving J, Beresten S, Ellis NA and Campisi J . (2001). J. Cell Biol., 153, 367–380.

  • Bootsma D and Hoeijmakers JH . (1993). Nature, 363, 114–115.

  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW and Vogelstein B . (1998). Science, 282, 1497–1501.

  • Chan JY, Li L, Fan YH, Mu ZM, Zhang WW and Chang KS . (1997). Biochem. Biophys. Res. Commun., 240, 640–646.

  • Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S and Borden KL . (2001). EMBO J., 20, 4547–4559.

  • Conchello JA, Kim JJ and Hansen EW . (1994). Appl. Opt., 33, 3740–3750.

  • de Boer J and Hoeijmakers JH . (2000). Carcinogenesis, 21, 453–460.

  • de The H, Lavau C, Marchio A, Chomienne C, Degos L and Dejean A . (1991). Cell, 66, 675–684.

  • Ellis NA, Ciocci S and German J . (2001). Hum. Genet., 108, 167–173.

  • Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M and German J . (1995). Cell, 83, 655–666.

  • Ellis NA, Proytcheva M, Sanz MM, Ye TZ and German J . (1999). Am. J. Hum. Genet., 65, 1368–1374.

  • Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C and 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 and Del Sal G . (2000). EMBO J., 19, 6185–6195.

  • Ford JM and Hanawalt PC . (1997). J. Biol. Chem., 272, 28073–28080.

  • German J . (1993). Medicine (Baltimore), 72, 393–406.

  • Gottifredi V and Prives C . (2001). Trends Cell Biol., 11, 184–187.

  • Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W and Paolo PP . (2000). Nat. Cell Biol., 2, 730–736.

  • Hu P, Beresten S, van Brabant A, Ye TZ, Pandolfi PP, Johnson FB, Guarente L and Ellis NA . (2001). Hum. Mol. Genet., 10, 1287–1298.

  • Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss III JF and Maul GG . (1999). J. Cell Biol., 147, 221–234.

  • Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A, Duprez E, Pandolfi PP, Puvion E, Freemont P and de The H . (2001). J. Exp. Med., 193, 1361–1372.

  • Leveillard T, Andera L, Bissonnette N, Schaeffer L, Bracco L, Egly JM and Wasylyk B . (1996). EMBO J, 15, 1615–1624.

  • Maul GG, Negorev D, Bell P and Ishov AM . (2000). J. Struct. Biol., 129, 278–287.

  • Maul GG, Yu E, Ishov AM and Epstein AL . (1995). J. Cell Biochem., 59, 498–513.

  • Melnick A and Licht JD . (1999). Blood, 93, 3167–3215.

  • Negorev D and Maul GG . (2001). Oncogene, 20, 7234–7242.

  • Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP and Pelicci PG . (2000). Nature, 406, 207–210.

  • Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC and de The H . (1998). Nat. Genet., 20, 259–265.

  • Robles AI, Wang XW and Harris CC . (1999). Oncogene, 18, 4681–4688.

  • Rubbi CP and Milner J . (2000). Oncogene, 19, 85–96.

  • Rubbi CP and Milner J . (2001). Carcinogenesis, 22, 1789–1796.

  • Ruggero D, Wang ZG and Pandolfi PP . (2000). Bioessays, 22, 827–835.

  • Salomoni P and Pandolfi PP . (2002). Cell, 108, 165–170.

  • Sanz MM, Proytcheva M, Ellis NA, Holloman WK and German J . (2000). Cytogenet. Cell Genet., 91, 217–223.

  • Stadler M, Chelbi-Alix MK, Koken MH, Venturini L, Lee C, Saib A, Quignon F, Pelicano L, Guillemin MC and Schindler C . (1995). Oncogene, 11, 2565–2573.

  • Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L and van Driel R . (1992). J. Cell. Sci., 101(Part 4), 773–784.

  • Tchang F and Mechali M . (1999). Exp. Cell Res., 251, 46–56.

  • Vallian S, Chin KV and Chang KS . (1998). Mol. Cell Biol., 18, 7147–7156.

  • van Brabant AJ, Stan R and Ellis NA . (2000). Annu. Rev. Genom. Hum. Genet., 1, 409–459.

  • Vogelstein B, Lane D and Levine AJ . (2000). Nature, 408, 307–310.

  • Wang W, Seki M, Narita Y, Sonoda E, Takeda S, Yamada K, Masuko T, Katada T and Enomoto T . (2000). EMBO J., 19, 3428–3435.

  • Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S and Harris CC . (2001). J. Biol. Chem., 276, 32948–32955.

  • Wang XW, Vermeulen W, Coursen JD, Gibson M, Lupold SE, Forrester K, Xu G, Elmore L, Yeh H, Hoeijmakers JHJ and Harris CC . (1996). Genes Dev., 10, 1219–1232.

  • Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG, Bohr VA, Weeda G, Hoeijmakers JH, Forrester K and Harris CC . (1995). Nat. Genet., 10, 188–195.

  • Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R and Pandolfi PP . (1998). Nat. Genet., 20, 266–272.

  • Wood RD . (1997). J. Biol. Chem., 272, 23465–23468.

  • Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S and Chang KS . (2001). Mol. Cell Biol., 21, 2259–2268.

  • Yankiwski V, Noonan JP and Neff NF . (2001). BMC Cell Biol., 2, 11.

  • Zhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC and Fornace Jr AJ (1999). Oncogene, 18, 2892–2900.

  • Zhong S, Hu P, Ye TZ, Stan R, Ellis NA and Pandolfi PP . (1999). Oncogene, 18, 7941–7947.

  • Zhong S, Salomoni P and Pandolfi PP . (2000). Nat. Cell Biol., 2, E85–E90.

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Acknowledgements

We thank Dorothea Dudek for editorial, Judith A Welsh for graphical, and Karen MacPherson for bibliographic assistance. HS was supported, in part, by a DFG Fellowship, award no. SE 978/11.

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Author notes

  1. Hasan Seker and Carlos Rubbi: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, 20892-4255, MD, USA

    Hasan Seker, Steven P Linke, Elise D Bowman & Curtis C Harris

  2. Biology Department, YCR p53 Laboratory, University of York, York, YO1 5DD, UK

    Carlos Rubbi & Jo Milner

  3. Laboratory of Experimental Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, 20892, MD, USA

    Susan Garfield

  4. Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, 68178, NE, USA

    Laura Hansen

  5. Department of Physiology and Biophysics, Structural Biology Program, Mt Sinai School of Medicine, New York, 10029, NY, USA

    Katherine LB Borden

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  1. Hasan Seker
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  2. Carlos Rubbi
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  8. Jo Milner
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  9. Curtis C Harris
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Correspondence to Curtis C Harris.

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Seker, H., Rubbi, C., Linke, S. et al. UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML. Oncogene 22, 1620–1628 (2003). https://doi.org/10.1038/sj.onc.1206140

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  • DOI: https://doi.org/10.1038/sj.onc.1206140

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