INVESTIGADORES
CERUTI Julieta Maria
congresos y reuniones científicas
Título:
ING1B TUMOR SUPPRESSOR REQUIRES FUNCTIONAL
Autor/es:
CERUTI, JM; OGARA, MF; PALMERO, IGNACIO; CÁNEPA E T
Reunión:
Congreso; XLVII SAIB; 2011
Institución organizadora:
SAIB
Resumen:
ING1B TUMOR SUPPRESSOR REQUIRES FUNCTIONAL
CHECKPOINT KINASE 1 TO EXERT ITS DNA REPAIR
ACTIVITY
Ceruti JM1, Ogara MF1, 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), a member of the ING protein
family, is involved in senescence, cell cycle arrest, apoptosis and
DNA repair. Here, we studied the role of endogenous ING1b in
DNA repair, in wild type and Ing1 deficient g/g MEFs, treated with
H O or neocarzinostatin (NCS) as genotoxic agents. In absence of 2 2
ING1 DNA repair is impaired in
assays for both treatments. Moreover, transfection of Ing1b
antisense oligonucleotide in wt MEFs reduced DNA repair to levels
in g/g MEFs. g/g MEFs showed higher levels of gH2AX, a marker
of DSBs, relative to wt MEFs. These displayed a slower kinetics of
gH2AX appearance than g/g MEFs indicating that ING1b
deficiency results in an exacerbated response to DNA damage. We
showed that ING1b transcript and protein are up-regulated by H O , 2 2
NCS and UV in MEFs, HCT116 and H1299 cells and this induction
is independent of p53. We also detected ING1b phosphorylation in
HCT116 cells by metabolic labelling after DNA damage,
independently of p53. Moreover, ING1b DNA repair activity in wt
MEFs is completely abolished when Chk1 is inhibited by
SB218078. In summary, ING1b improves DNA repair in response
to a variety of genotoxic agents. We propose that physiological
levels of ING1b are required to trigger a proper DNA damage
response. Finally, phosphorylation of ING1b, probably by Chk1 is
necessary to exert its DNA repair activity.