Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Association of p53 and MSH2 with recombinative repair complexes during S phase

Oncogene volume 21, pages 4788–4800 (2002)Cite this article

A Corrigendum to this article was published on 09 May 2003

Abstract

Our previous recombination and biochemical analyses have led to the hypothesis that the tumor suppressor p53 monitors homologous recombination, a function which was previously attributed to the mismatch repair protein MSH2. Here, we show that a certain fraction of p53 is concentrated within discrete nuclear foci of cells synchronized in G1 phase, a pattern which becomes even more pronounced in S phase, especially after γ-ray treatment. p53 foci show some colocalization with MSH2 within distinct foci during G1 phase, while dots formed by BRCA1 display an independent localization pattern. In S phase nuclei, p53 foci almost completely colocalize with MSH2 foci and associate with the recombination surveillance factor BRCA1 in irradiated S phase cells. These p53 and MSH2 foci also show significant overlaps with foci of the recombination enzymes Rad50 and Rad51, which for the first time unveiled recombination-related functions of p53 in replicating cells. During S phase, p53 and MSH2 are maximally active in binding to early recombination intermediates, and coexist within the same nuclear DNA-protein complexes. Our data suggest that p53 is linked similarly to homologous recombination as MSH2 and provide further evidence for the new concept of a dual role of p53 in the regulation of growth and repair.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 6
Figure 2
Figure 3
Figure 4
Figure 5
Figure 9
Figure 7
Figure 8

Similar content being viewed by others

References

  • Abraham J, Kelly J, Thibault P, Benchimol S . 2000 J. Mol. Biol. 295: 853–864

  • Alani E, Lee S, Kane MF, Griffith J, Kolodner RD . 1997 J. Mol. Biol. 265: 289–301

  • Albrechtsen N, Dornreiter I, Grosse F, Kim E, Wiesmüller L, Deppert W . 1999 Oncogene 18: 7706–7717

  • Baumann P, West SC . 1998 Trends Biochem. Sci. 23: 247–251

  • Bertrand P, Rouillard D, Boulet A, Levalois C, Soussi T, Lopez BS . 1997 Oncogene 14: 1117–1122

  • Cranston A, Bocker T, Reitmair A, Palazzo J, Wilson T, Mak T, Fishel R . 1997 Nature Genet. 17: 114–118

  • De Wind N, Dekker M, Berns A, Radman M, te Riele H . 1995 Cell 82: 321–330

  • Dignam JD, Lebovitz RM, Roeder RG . 1983 Nucleic Acids Res. 11: 1475–1489

  • Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JHJ . 1996 Mol. Cell. Biol. 16: 4832–4841

  • Donehower LA, Harvey M, Sladge BL, McArthur MJ, Montgomery CA, Butel JS, Bradley A . 1992 Nature 356: 215–221

  • Duckett DR, Bronstein SM, Taya Y, Modrich Y . 1999 Proc. Natl. Acad. Sci. USA 96: 12384–12388

  • Dudenhöffer C, Rohaly G, Will K, Deppert W, Wiesmüller L . 1998 Mol. Cell. Biol. 18: 5332–5342

  • Dudenhöffer C, Kurth M, Janus F, Deppert W, Wiesmüller L . 1999 Oncogene 18: 5773–5784

  • Durant ST, Morris MM, Illand M, McKay HJ, McCormick C, Hirst GL, Borts BH, Brown R . 1999 Curr. Biol. 9: 51–54

  • Eils R, Dietzel S, Bertin E, Schroeck E, Speicher MR, Ried T, Robert-Nicoud M, Cremer C, Cremer T . 1996 J. Cell. Biol. 135: 1427–1440

  • Evans E, Sugawara N, Haber JE, Alani E . 2000 Mol. Cell 5: 789–799

  • Fishel R . 1999 Nature Med. 5: 1239–1241

  • Flores-Rozas H, Kolodner RD . 2000 Trends Biochem. Sci. 25: 196–200

  • Flygare J, Benson F, Hellgren D . 1996 Biochim. Biophys. Acta 1312: 231–236

  • Gebow D, Miselis N, Liber HL . 2000 Mol. Cell. Biol. 20: 4028–4035

  • Gottifredi V, Shieh S-Y, Taya Y, Prives C . 2001 Proc. Natl. Acad. Sci. USA 98: 1036–1041

  • Gradia S, Acharya S, Fishel R . 1997 Cell 91: 995–1005

  • Haber J . 1998 Cell 95: 583–586

  • Hakem R, de la Pompa JL, Elia A, Potter J, Mak TW . 1997 Nature Genet. 16: 298–302

  • Harlow E, Crawford LV, Pim DC, Williamson NM . 1981a J. Virol. 9: 861–869

  • Harlow E, Pim DC, Crawford LV . 1981b J. Virol. 37: 564–573

  • Hollstein M, Rice K, Greenblatt MS, Soussi T, Fuchs R, Sorlie T, Hovig E, Smithsorensen B, Montesano R, Harris CC . 1994 Nucleic Acids Res. 22: 3551–3555

  • Huang P . 1998 Oncogene 17: 261–270

  • Hupp TR, Lane DP . 1994 Cold Spring Harb. Symp. Quant. Biol. 59: 195–206

  • Ishizaki K, Ejima Y, Matsunaga T, Hara R, Sakamoto A, Ikenaga M, Ikawa Y, Aizawa S . 1994 Int. J. Cancer 58: 254–257

  • Janz C, Süsse S, Wiesmüller L . 2002 Oncogene 21: 2130–2140

  • Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV . 1999 Science 85: 1733–1737

  • Kühn C, Müller F, Melle C, Nasheuer HP, Janus F, Deppert W, Grosse F . 1999 Oncogene 18: 769–774

  • Lambert S, Saintigny Y, Delacote F, Amiot F, Chaput B, Lecomte M, Huck S, Bertrand P, Lopez BS . 1999 Mutat. Res. 433: 159–168

  • Lane DP . 1992 Nature 358: 15–16

  • Levine A . 1997 Cell 88: 323–331

  • Lim D-S, Hasty P . 1996 Mol. Cell. Biol. 16: 7133–7143

  • Lin X, Ramamurthi K, Mishima M, Kondo A, Howell SB . 2000 Mol. Pharmacol. 58: 1222–1229

  • Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD . 1992 Cell 70: 923–935

  • Marsischky GT, Lee S, Griffith J, Kolodner RD . 1999 J. Biol. Chem. 274: 7200–7206

  • Mekeel KL, Tang W, Kachnic LA, Luo C-M, DeFrank JS, Powell SN . 1997 Oncogene 14: 1847–1857

  • Modrich P, Lahue R . 1996 Annu. Rev. Biochem. 65: 101–133

  • Moynahan ME, Chiu JW, Koller BH, Jasin M . 1999 Mol. Cell 4: 511–518

  • Nelms BE, Maser RS, MacKay JF, Lagally MG, Petrini JHJ . 1998 Science 280: 590–592

  • Orlando V, Paro R . 1993 Cell 75: 1187–1198

  • Raderschall E, Golub EI, Haaf T . 1999 Proc. Natl. Acad. Sci. USA 96: 1921–1926

  • Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, Waterhouse P, Mittrücker H-W, Wakeham A, Liu B, Thomason A, Griesser H, Gallinger S, Ballhausen WG, Fishel R, Mak TW . 1995 Nature Genet. 11: 64–70

  • Saintigny Y, Rouillard D, Chaput B, Soussi T, Lopez BS . 1999 Oncogene 18: 3553–3565

  • Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D, Lopez B . 2001 EMBO J. 20: 3861–3870

  • Saintigny Y, Lopez BS . 2002 Oncogene 21: 488–492

  • Scherer SJ, Maier SM, Seifert M, Hanselmann RG, Zang KD, Müller-Hermelink HK, Angel P, Welter C, Schartl M . 2000 J. Biol. Chem. 275: 37469–37473

  • Schirmbeck R, Deppert W . 1989 J. Virol. 63: 2308–2316

  • Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM . 1997a Cell 88: 265–275

  • Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM . 1997b Cell 90: 425–435

  • Süsse S, Janz C, Janus F, Deppert W, Wiesmüller L . 2000 Oncogene 19: 4500–4512

  • Tashiro S, Kotomura N, Shinohara A, Tanaka K, Ueda K, Kamada N . 1996 Oncogene 12: 2165–2170

  • Tashiro S, Walter J, Shinohara A, Kamada N, Cremer T . 2000 J. Cell Biol. 150: 283–291

  • Venkitaraman AR . 1999 Science 286: 1100–1102

  • Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J . 2000 Genes Dev. 14: 927–939

  • Whitby MC, Lloyd RG . 1995 EMBO J. 14: 3302–3310

  • Wiesmüller L, Cammenga J, Deppert W . 1996 J. Virol. 70: 737–744

  • Willers H, McCarthy EE, Wu B, Wunsch H, Tang W, Taghian DG, Xia F, Powell SN . 2000 Oncogene 19: 632–639

  • Yamada M, O'Regan E, Brown R, Karran P . 1997 Nucleic Acids Res. 25: 491–495

  • Vaughn JP, Davis PL, Jarboe MD, Huper G, Evans AC, Wiseman RW, Berchuck A, Iglehart JD, Futreal PA, Marks JR . 1996 Cell Growth Differ. 7: 711–715

  • Zhong Q, Chen C-F, Li S, Chen Y, Wang C-C, Xiao J, Chen P-L, Sharp ZD, Lee W-H . 1999 Science 285: 747–750

  • Zhou J, Ahn J, Wilson SH, Prives C . 2001 EMBO J. 20: 914–923

Download references

Acknowledgements

We are especially indebted to Prof Dr John HJ Petrini, University of Wisconsin Medical School, Madison, and to Akira Shinohara, Osaka University, for supplying Rad50 and Rad51 antiserum, respectively. We thank Evelyn Bendrat for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft, grants Wi 1376/1-4 and -5 and grant 10-1281-Wi I by the Deutsche Krebshilfe, the Dr Mildred Scheel Stiftung.

Author information

Authors and Affiliations

  1. Institut für Anthropologie und Humangenetik LMU München, Goethestr, 31,80336, München, Germany

    Daniele Zink & Christoph Mayr

  2. Universitätsfrauenklinik und Poliklinik, Prittwitzstrasse 43, Ulm, D-89075, Germany

    Christine Janz & Lisa Wiesmüller

Authors
  1. Daniele Zink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Mayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Janz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lisa Wiesmüller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christine Janz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zink, D., Mayr, C., Janz, C. et al. Association of p53 and MSH2 with recombinative repair complexes during S phase. Oncogene 21, 4788–4800 (2002). https://doi.org/10.1038/sj.onc.1205614

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205614

Keywords

This article is cited by

Search

Advanced search

Quick links