INVESTIGADORES
CANEPA Eduardo Tomas
artículos
Título:
Cell cycle inhibitor, p19INK4d, promotes cell survival and decreases chromosomal aberrations after genotoxic insult due to enhanced DNA repair
Autor/es:
MARÍA E. SCASSA; MARIELA C. MARAZITA; JULIETA M. CERUTI; ABEL L. CARCAGNO; PABLO F. SIRKIN; MARCELA GONZÁLEZ-CID; OMAR P. PIGNATARO; EDUARDO T. CÁNEPA
Revista:
MUTATION RESEARCH-DNA REPAIR
Editorial:
Elsevier Science
Referencias:
Lugar: Amsterdam; Año: 2007 vol. 6 p. 626 - 638
ISSN:
0921-8777
Resumen:
Genome integrity and cell proliferation and survival are regulated by an intricate network
of pathways that includes cell cycle checkpoints, DNA repair and recombination, and programmed
cell death. It makes sense that there should be a coordinated regulation of these
different processes, but the components of such mechanisms remain unknown. In this
report, we demonstrate that p19INK4d expression enhances cell survival under genotoxic
conditions. By using p19INK4d-overexpressing clones, we demonstrated that p19INK4d
expression correlates with the cellular resistance to UV treatment with increased DNA
repair activity against UV-induced lesions. On the contrary, cells transfected with p19INK4d
antisense cDNA show reduced ability to repair DNA damage and increased sensitivity to
genotoxic insult when compared with their p19INK4d-overexpressing counterparts. Consistent
with these findings, our studies also show that p19INK4d-overexpressing cells present
not only a minor accumulation of UV-induced chromosomal aberrations but a lower frequency
of spontaneous chromosome abnormalities than p19INK4d-antisense cells. Lastly,
we suggest that p19INK4d effects are dissociated from its role as CDK4/6 inhibitor. The
results presented herein support a crucial role for p19INK4d in regulating genomic stability
and overall cell viability under conditions of genotoxic stress. We propose that p19INK4d
would belong to a protein network that would integrate DNA repair, apoptotic and checkpoint
mechanisms in order to maintain the genomic integrity.