Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways

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 r...

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Publicado:	2013
Materias:	Checkpoint kinase 1 Chromatin structure DNA damage response DNA repair Genotoxic stress ING1 P53 beta tubulin gamma H2AX histone H2AX hydrogen peroxide inhibitor of growth 1 protein messenger RNA mutant protein protein ING1b protein p16 protein p21 protein p53 trichostatin A tumor suppressor protein unclassified drug zinostatin checkpoint kinase 1 gamma H2AX protein, mouse gamma-H2AX protein, mouse histone ING1 protein, human isoprotein nuclear protein protein kinase signal peptide animal cell apoptosis article cell cycle arrest cell type controlled study DNA damage gene expression regulation human human cell Ing1b gene nonhuman protein domain protein expression senescence transcription regulation tumor growth tumor suppressor gene upregulation wild type animal gene expression genomic instability human genome metabolism missense mutation mouse physiology tumor cell line Animals Cell Line, Tumor DNA Damage DNA Repair Gene Expression Genome, Human Genomic Instability Histones Humans Intracellular Signaling Peptides and Proteins Mice Mutation, Missense Nuclear Proteins Protein Isoforms Protein Kinases Tumor Suppressor Proteins Up-Regulation
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v378_n1-2_p117_Ceruti http://hdl.handle.net/20.500.12110/paper_03008177_v378_n1-2_p117_Ceruti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_03008177_v378_n1-2_p117_Ceruti2023-06-08T15:27:27Z Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways Checkpoint kinase 1 Chromatin structure DNA damage response DNA repair Genotoxic stress ING1 P53 beta tubulin gamma H2AX histone H2AX hydrogen peroxide inhibitor of growth 1 protein messenger RNA mutant protein protein ING1b protein p16 protein p21 protein p53 trichostatin A tumor suppressor protein unclassified drug zinostatin checkpoint kinase 1 gamma H2AX protein, mouse gamma-H2AX protein, mouse histone ING1 protein, human isoprotein nuclear protein protein kinase signal peptide tumor suppressor protein animal cell apoptosis article cell cycle arrest cell type controlled study DNA damage DNA repair gene expression regulation human human cell Ing1b gene nonhuman protein domain protein expression senescence transcription regulation tumor growth tumor suppressor gene upregulation wild type animal gene expression genomic instability human genome metabolism missense mutation mouse physiology tumor cell line Animals Cell Line, Tumor DNA Damage DNA Repair Gene Expression Genome, Human Genomic Instability Histones Humans Intracellular Signaling Peptides and Proteins Mice Mutation, Missense Nuclear Proteins Protein Isoforms Protein Kinases Tumor Suppressor Proteins Up-Regulation 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 H 2O2 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. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v378_n1-2_p117_Ceruti http://hdl.handle.net/20.500.12110/paper_03008177_v378_n1-2_p117_Ceruti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Checkpoint kinase 1 Chromatin structure DNA damage response DNA repair Genotoxic stress ING1 P53 beta tubulin gamma H2AX histone H2AX hydrogen peroxide inhibitor of growth 1 protein messenger RNA mutant protein protein ING1b protein p16 protein p21 protein p53 trichostatin A tumor suppressor protein unclassified drug zinostatin checkpoint kinase 1 gamma H2AX protein, mouse gamma-H2AX protein, mouse histone ING1 protein, human isoprotein nuclear protein protein kinase signal peptide tumor suppressor protein animal cell apoptosis article cell cycle arrest cell type controlled study DNA damage DNA repair gene expression regulation human human cell Ing1b gene nonhuman protein domain protein expression senescence transcription regulation tumor growth tumor suppressor gene upregulation wild type animal gene expression genomic instability human genome metabolism missense mutation mouse physiology tumor cell line Animals Cell Line, Tumor DNA Damage DNA Repair Gene Expression Genome, Human Genomic Instability Histones Humans Intracellular Signaling Peptides and Proteins Mice Mutation, Missense Nuclear Proteins Protein Isoforms Protein Kinases Tumor Suppressor Proteins Up-Regulation
spellingShingle	Checkpoint kinase 1 Chromatin structure DNA damage response DNA repair Genotoxic stress ING1 P53 beta tubulin gamma H2AX histone H2AX hydrogen peroxide inhibitor of growth 1 protein messenger RNA mutant protein protein ING1b protein p16 protein p21 protein p53 trichostatin A tumor suppressor protein unclassified drug zinostatin checkpoint kinase 1 gamma H2AX protein, mouse gamma-H2AX protein, mouse histone ING1 protein, human isoprotein nuclear protein protein kinase signal peptide tumor suppressor protein animal cell apoptosis article cell cycle arrest cell type controlled study DNA damage DNA repair gene expression regulation human human cell Ing1b gene nonhuman protein domain protein expression senescence transcription regulation tumor growth tumor suppressor gene upregulation wild type animal gene expression genomic instability human genome metabolism missense mutation mouse physiology tumor cell line Animals Cell Line, Tumor DNA Damage DNA Repair Gene Expression Genome, Human Genomic Instability Histones Humans Intracellular Signaling Peptides and Proteins Mice Mutation, Missense Nuclear Proteins Protein Isoforms Protein Kinases Tumor Suppressor Proteins Up-Regulation Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
topic_facet	Checkpoint kinase 1 Chromatin structure DNA damage response DNA repair Genotoxic stress ING1 P53 beta tubulin gamma H2AX histone H2AX hydrogen peroxide inhibitor of growth 1 protein messenger RNA mutant protein protein ING1b protein p16 protein p21 protein p53 trichostatin A tumor suppressor protein unclassified drug zinostatin checkpoint kinase 1 gamma H2AX protein, mouse gamma-H2AX protein, mouse histone ING1 protein, human isoprotein nuclear protein protein kinase signal peptide tumor suppressor protein animal cell apoptosis article cell cycle arrest cell type controlled study DNA damage DNA repair gene expression regulation human human cell Ing1b gene nonhuman protein domain protein expression senescence transcription regulation tumor growth tumor suppressor gene upregulation wild type animal gene expression genomic instability human genome metabolism missense mutation mouse physiology tumor cell line Animals Cell Line, Tumor DNA Damage DNA Repair Gene Expression Genome, Human Genomic Instability Histones Humans Intracellular Signaling Peptides and Proteins Mice Mutation, Missense Nuclear Proteins Protein Isoforms Protein Kinases Tumor Suppressor Proteins Up-Regulation
description	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 H 2O2 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.
title	Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
title_short	Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
title_full	Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
title_fullStr	Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
title_full_unstemmed	Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways
title_sort	inhibitor of growth 1 (ing1) acts at early steps of multiple dna repair pathways
publishDate	2013
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v378_n1-2_p117_Ceruti http://hdl.handle.net/20.500.12110/paper_03008177_v378_n1-2_p117_Ceruti
_version_	1768542362340950016

Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways

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