A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.

<h4>Background</h4>The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals.<h4>Methodology/principal findings</h4>We have used a conditional null mutant mouse model in a...

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Autores principales:	Anna Melchers, Lars Stöckl, Janina Radszewski, Marco Anders, Harald Krenzlin, Candy Kalischke, Regina Scholz, Andreas Jordan, Grit Nebrich, Joachim Klose, Karl Sperling, Martin Digweed, Ilja Demuth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cdf537450a1d4aebbc16ca29599ebf77
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spelling	oai:doaj.org-article:cdf537450a1d4aebbc16ca29599ebf772021-11-25T06:22:53ZA systematic proteomic study of irradiated DNA repair deficient Nbn-mice.1932-620310.1371/journal.pone.0005423https://doaj.org/article/cdf537450a1d4aebbc16ca29599ebf772009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19412544/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals.<h4>Methodology/principal findings</h4>We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs.<h4>Conclusions/significance</h4>In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress.Anna MelchersLars StöcklJanina RadszewskiMarco AndersHarald KrenzlinCandy KalischkeRegina ScholzAndreas JordanGrit NebrichJoachim KloseKarl SperlingMartin DigweedIlja DemuthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 5, p e5423 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Melchers Lars Stöckl Janina Radszewski Marco Anders Harald Krenzlin Candy Kalischke Regina Scholz Andreas Jordan Grit Nebrich Joachim Klose Karl Sperling Martin Digweed Ilja Demuth A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
description	<h4>Background</h4>The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals.<h4>Methodology/principal findings</h4>We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs.<h4>Conclusions/significance</h4>In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress.
format	article
author	Anna Melchers Lars Stöckl Janina Radszewski Marco Anders Harald Krenzlin Candy Kalischke Regina Scholz Andreas Jordan Grit Nebrich Joachim Klose Karl Sperling Martin Digweed Ilja Demuth
author_facet	Anna Melchers Lars Stöckl Janina Radszewski Marco Anders Harald Krenzlin Candy Kalischke Regina Scholz Andreas Jordan Grit Nebrich Joachim Klose Karl Sperling Martin Digweed Ilja Demuth
author_sort	Anna Melchers
title	A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
title_short	A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
title_full	A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
title_fullStr	A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
title_full_unstemmed	A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.
title_sort	systematic proteomic study of irradiated dna repair deficient nbn-mice.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/cdf537450a1d4aebbc16ca29599ebf77
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A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.

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