ING1b tumor suppressor protects genome integrity from oxidative stress in MEFs

CERUTI, J. M.; OGARA, M.F.; CARCAGNO, A.L.; PALMERO, I.; CÁNEPA, E.T.

Villa Carlos Paz

Congreso; XLIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB); 2008

SOCIEDAD ARGENTINA DE INVESTIGACION EN BIOQUIMICA Y BIOLOGIA MOLECULAR (SAIB)

Inhibitor of Growth 1b (ING1b), is a member of the ING protein family involved in various biological functions ranging from senescence, cell cycle arrest, apoptosis to DNA repair. ING1 mutations and altered expression levels are found in multiple human cancers. We investigated the role of ING1b in the cellular response triggered by oxidative stress and IR. We first examined the level of gamma-H2AX in wild type or ING1b gene trap MEFs (GG MEFs) by western blot, after H2O2 treatment. Expression peak of this damage marker, and its remanent level along time are greater in GG MEFs. Similar results were obtained after IR treatment. It is reported that gamma-H2AX level and size of foci are greater in relaxed chromatin after DNA damage. ING1b can target HDAC complexes to particular domains of chromatin. When MEFs were treated with the inhibitor of HDACs, Trichostatine A, before IR, there was an increase in DNA damage for both cellular types as indicated by the phosphorylated H2AX level. It seems that the absence of ING1b has an effect on chromatin, similar to that of TSA, confirming the notion of ING1b functioning as a bridge between HDACs complexes and nucleosomes. Finally, in UDS assay, we observed that ING1b mutated in its PHD finger domain could not repair peroxide damaged DNA as the wild type protein does. These results confer ING1b a protective role to cells under oxidative stress.