INVESTIGADORES
CERUTI Julieta Maria
congresos y reuniones científicas
Título:
ING1B TUMOR SUPPRESSOR PROTECTS GENOME INTEGRITY FROM OXIDATIVE STRESS IN MEFS.
Autor/es:
JULIETA M. CERUTI; MARÍA F. OGARA; ABEL L. CARCAGNO; IGNACIO PALMERO; EDUARDO T. CÁNEPA
Lugar:
Villa Carlos Paz, Argentina
Reunión:
Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008
Institución organizadora:
SAIB
Resumen:
ING1b TUMOR SUPPRESSOR PROTECTS GENOME
INTEGRITY FROM OXIDATIVE STRESS IN MEFS
Ceruti JM1, Ogara MF1, Carcagno AL1, Palmero I2, Cánepa ET1.
1Depto. Química Biológica, FCEN, UBA, Argentina. 2Instituto
Investigaciones Biomédicas, UAM, España. E-mail:
julce@qb.fcen.uba.ar
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.