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:

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Oncogene volume 20, pages 3290–3300 (2001)Cite this article

Abstract

Cyclin G1 is one of the target genes of the transcription factor p53, and is induced in a p53-dependent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena, its precise function remains unclear. Here we present an analysis of the physiological role of cyclin G1 using mice homozygous for a targeted disruption of the cyclin G1 gene. In order to clarify the role of cyclin G1 in the p53 pathway, downstream events such as apoptosis, cell growth and cell cycle checkpoint control were analysed in thymocytes and embryonic fibroblasts derived from cyclin G1-disrupted mice. No difference was detected in induction of apoptosis between mouse embryo fibroblasts (MEFs) derived from cyclin G1+/+ and cyclin G1−/− mice. Following irradiation, cyclin G1−/− MEFs proliferated more slowly and reached lower cell densities in culture dishes than cyclin G1+/+ MEFs. Analysis of cell survival showed that cyclin G1−/− MEFs were about twice as sensitive as cyclin G1+/+ MEFs to γ radiation or UV radiation. Cyclin G1−/− mice were more sensitive to γ radiation than wild-type mice. Flow cytometeric analysis revealed that the number of cyclin G1−/− MEFs in G2/M phase after irradiation was reduced by 50% relative to cyclin G1+/+ MEFs. Our results demonstrate that cyclin G1 plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress.

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 3
Figure 2
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Amundson SA, Myers TG, Fornace Jr AJ . 1998 Oncogene 17: 3287–3299

  • Asahina H, Han Z-B, Kawanishi M, Kato Jr T, Ayaki H, Todo T, Yagi T, Takebe H, Ikenaga M, Kimura SH . 1999 Mutation Res. 435: 255–262

  • Attardi LD, Lowe SW, Brugarolas J, Jack T . 1996 EMBO J. 15: 3693–3701

  • Barak Y, Juven T, Haffner R, Oren M . 1993 EMBO J. 12: 461–468

  • Bates S, Vousden KH . 1999 Cell Mol. Life Sci. 55: 28–47

  • Bates S, Rowan S, Vousden KH . 1996 Oncogene 13: 1103–1109

  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ . 1995 Nature 377: 552–557

  • Choisy Rossi C, Reisdorf P, Yonish Rouach E . 1998 Toxicol. Let. 102–103: 491–496

  • Dameron KM, Volpert OV, Tainsky MA, Bouck N . 1994 Science 265: 1582–1584

  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P . 1995 Cell 82: 675–684

  • Ding HF, Fisher DE . 1998 Crit. Rev. Oncog. 9: 83–98

  • Edwards MC, Wong C, Elledge SJ . 1998 Mol. Cell. Biol. 18: 4291–4300

  • El-Deiry WS . 1998 Curr. Top. Microbiol. Immunol. 227: 121–137

  • Fantes P, Brooks R . 1993 The Cell Cycle: A Practical Approach IRL Press: Oxford pp 6–9

    Google Scholar 

  • Fu TJ, Peng J, Lee G, Price DH, Flores O . 1999 J. Biol. Chem. 274: 34527–34530

  • Giaccia AJ, Kastan MB . 1998 Genes Dev. 12: 2973–2983

  • Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, Kinzler KW, Vogelstein B . 1997 Mol. Cell 1: 3–11

  • Horne MC, Donaldson KL, Goolsby GL, Tran D, Mulheisen M, Hell JW, Wahl AF . 1997 J. Biol. Chem. 272: 12650–12661

  • Horne MC, Goolsby GL, Donaldson KL, Tran D, Neubauer M, Wahl AF . 1996 J. Biol. Chem. 271: 6050–6061

  • Hunter T . 1991 Semin. Cell Biol. 2: 213–222

  • Ikawa M, Wada I, Kominami K, Watanabe D, Toshimori K, Nishimune Y, Okabe M . 1997 Nature 387: 607–611

  • Janus F, Albrechtsen N, Dornreiter I, Wiesmuller L, Grosse F, Deppert W . 1999 Cell Mol. Life Sci. 55: 12–27

  • Jayaraman L, Prives C . 1999 Cell Mol. Life Sci. 55: 76–87

  • Kanaoka Y, Kimura SH, Okazaki I, Ikeda M, Nojima H . 1997 FEBS Lett. 402: 73–80

  • Kemp CJ, Wheldon T, Balmain A . 1994 Nature Genet. 8: 66–69

  • Kimura SH, Kataoka TR, Endo Y, Nojima H . 1997a Geonomics 46: 483–486

  • Kimura SH, Tsuruga H, Yabuta N, Endo Y, Nojima H . 1997b Genomics 44: 179–187

  • Kong M, Barnes EA, Ollendorff V, Donoghue DJ . 2000 EMBO J. 19: 1378–1388

  • Levine AJ . 1997 Cell 88: 323–331

  • Miyashita T, Reed JC . 1995 Cell 80: 293–299

  • Morgenstern JP, Land H . 1990 Nucleic Acids Res. 18: 3587–3596

  • Morita N, Kiryu S, Kiyama H . 1996 J. Neurosci. 16: 5961–5966

  • Nakamura T, Sanokawa R, Saski RS, Ayusawa D, Oishi M, Mori N . 1995 Exp. Cell Res. 221: 534–542

  • Okamoto K, Beach D . 1994 EMBO J. 13: 4816–4822

  • Okamoto K, Kamibayashi C, Serrano M, Prives C, Mumby MC, Beach D . 1996 Mol. Cell. Biol. 16: 6593–6602

  • Okamoto K, Prives C . 1999 Oncogene 18: 4606–4615

  • Pear WS, Nolan GP, Scott ML, Baltimore D . 1993 Proc. Natl. Acad. Sci. USA 90: 8392–8396

  • Pines J . 1991 Cell Growth Differ. 2: 305–310

  • Pines J, Hunter T . 1989 Cell 58: 833–846

  • Reimer CL, Borras AM, Kurdistani SK, Garreau JR, Chung M, Aaronson SA, Lee SW . 1999 J. Biol. Chem. 274: 11022–11029

  • Robertson EJ . 1987 Teratocarcinoma and Embryonic Stem Cells, A Practical Approach IRL Press: Oxford pp 77–78

    Google Scholar 

  • Sabbatini P, Lin J, Levine AJ, White E . 1995 Genes Dev. 9: 2184–2192

  • Sambrook J, Fritsch EF, Maniatis T . 1989 Molecular cloning. A Laboratory manual Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY

    Google Scholar 

  • Shimizu A, Nishida J, Ueoka Y, Kato K, Hachiya T, Kuiaki Y, Wake N . 1998 Biochem. Biophys. Res. Commun. 242: 529–533

  • Sionov RV, Haupt Y . 1999 Oncogene 18: 6145–6157

  • Skotzko M, Wu L, Anderson WF, Gordon EM, Hall FL . 1995 Cancer Res. 55: 5493–5498

  • Smith ML, Chen I-T, Zhan Q, Bae I, Chen C-Y, Gilmer TM, Kastan MB, O'Connor PM, Fornace Jr AJ . 1994 Science 266: 1376–1379

  • Smith ML. Kontny HU, Bortnick R, Fornace Jr AJ . 1997 Exp. Cell Res. 230: 61–68

  • Tamura K, Kanaoka Y, Jinno S, Nagata A, Ogiso Y, Shimizu K, Hayakawa T, Nojima H, Okayama H . 1993 Oncogene 8: 2113–2118

  • Tybulewicz VLJ, Crawford CE, Jackson PK, Bronson RT, Mulligan RC . 1991 Cell 65: 1153–1163

  • Wei P, Garber ME, Fang SM, Fischer WH, Jones KA . 1998 Cell 92: 451–462

  • Wu X, Bayle H, Olson D, Levine AJ . 1993 Genes Dev. 7: 1126–1132

  • Zauberman A, Lupo A, Oren M . 1995 Oncogene 10: 2361–2366

Download references

Acknowledgements

We thank Ms Kaori Yamauchi, Mr Tatsuki R Kataoka and Mr Yuichiro Koma for technical assistance and Dr Naohisa Yoshioka for the retroviral vector, pBabe-Puro. This work was supported by grants from the Ministry of Education, Science and Culture, Japan and grants from the Osaka Cancer Society, Uehara Foundation, Yasuda Medical Research Foundation, Welfide Medical Research Foundation and Osaka Cancer Research Foundation.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Shinya H Kimura & Hiroshi Nojima

  2. Genome Information Research Center, Osaka University, 3-1 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Masahito Ikawa & Masaru Okabe

  3. Department of Pathology, Medical School, Osaka University, 3-1 Yamadaoka, Suita, 5650-0871, Osaka, Japan

    Akihiko Ito

Authors
  1. Shinya H Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahito Ikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akihiko Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masaru Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Nojima
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kimura, S., Ikawa, M., Ito, A. et al. Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery. Oncogene 20, 3290–3300 (2001). https://doi.org/10.1038/sj.onc.1204270

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204270

Keywords

This article is cited by

Search

Advanced search

Quick links