Biopolym. Cell. 2019; 35(3):184-185.
Chronicle and Information
ING3 is required for ATM signaling and DNA repair in response to DNA double strand breaks
1Mouche A., 1Archambeau J., 1Ricordel C., 1, 4Chaillot L., 2, 3Bigot N., 1, 4Guillaudeux T., 5Grenon M., 1Pedeux R.
  1. INSERM U1242, COSS, Université de Rennes 1, CLCC Eugène Marquis
    Rennes, France
    Rennes, France
  3. Genome Damage and Stability Centre, University of Sussex
    Falmer, Brighton BN1 9RQ, UK
  4. UMS Biosit, SFR Biologie-Santé
    Rennes, France
  5. Biochemistry, School of Natural Sciences, National University of Ireland
    Galway, Ireland


ING3 (Inhibitor of Growth 3) is a candidate tumor suppressor gene whose expression is lost in tumors. Aims: We want to identify and characterize new tumor suppresor functions for ING3. Methods: We conduct experiments in yeast and human cells depleted or not for ING3 and exposed to genotoxic agents. Results: - ING3-depleted human cells and yeast cells deleted for its ortholog YNG2 are sensitive to DNA damage suggesting a conserved role in response to such stress. - In human cells, ING3 is recruited to DNA double strand breaks and is required for ATM activation. - In response to doxorubicin, ATM activation is dependent on ING3 but not on TIP60, whose recruitment to DNA breaks also depends on ING3. - These events lead to ATM-mediated phosphorylation of NBS1 and of major mediators of the DNA damage response. - Upon genotoxic stress, DNA repair by Non Homologous End Joining (NHEJ) or Homologous Recombination (HR) were impaired in absence of ING3. - Immunoglobulin Class Switch Recombination (CSR), a physiological mechanism requiring NHEJ repair, was impaired in the absence of ING3. Conclusions: Since deregulation of DNA double strand break repair is associated with genomic instability, we propose a novel function of ING3 as a caretaker tumor suppressor involved in the DNA damage signaling and repair. Funding: A.M. was a recipient of a doctoral fellowship from La Ligue Contre le Cancer and Region Bretagne. R.P. & M.G. were recipients of from Ulysses “The France – Ireland Exchange Scheme”. N. Bigot was a recipient of ANR program (SAFE 2012) (ANR-11-RPIB-0012). C. References: Cell Death Differ. 2019 Feb 25. doi: 10.1038/s41418-019-0305-x. [Epub ahead of print]