2024-03-28T21:24:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/782442016-02-17T16:22:55Zcom_10261_22com_10261_1col_10261_275
Menéndez, Camino
Palmero, Ignacio
2013-06-18T10:36:16Z
2013-06-18T10:36:16Z
2013-06
Molecular and Cellular Biochemistry 378(1-2): 117-126 (2013)
0300-8177
http://hdl.handle.net/10261/78244
10.1007/s11010-013-1601-2
1573-4919
http://dx.doi.org/10.13039/501100002923
http://dx.doi.org/10.13039/501100003074
http://dx.doi.org/10.13039/501100005363
http://dx.doi.org/10.13039/501100004837
ING proteins are tumor suppressors involved in the regulation of gene transcription, cell cycle arrest, apoptosis, and senescence. Here, we show that ING1b expression is upregulated by several DNA-damaging agents, in a p53-independent manner. ING1b stimulates DNA repair of a variety of DNA lesions requiring activation of multiple DNA repair pathways. Moreover, Ing1 −/− cells showed impaired genomic DNA repair after H2O2 and neocarzinostatin treatment and this defect was reverted by overexpression of ING1b. Two tumor-derived ING1 mutants failed to promote DNA repair highlighting the physiological importance of the integrity of the PHD domain for ING1b DNA repair activity and suggesting a role in the prevention of tumor progression. Ing−/− cells showed higher basal levels of γ-H2AX and, upon DNA damage, γ-H2AX increase was greater and with faster kinetics compared to wild-type cells. Chromatin relaxation by Trichostatin A led to an exacerbated damage signal in both types of cells, but this effect was dependent on Ing1 status, and more pronounced in wild-type cells. Our results suggest that ING1 acts at early stages of the DNA damage response activating a variety of repair mechanisms and that this function of ING1 is targeted in tumors.
eng
closedAccess
ING1
DNA repair
p53
Chromatin structure
Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
artículo