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Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation

Human glioblastomas are characterized by frequent DNA amplifications most often at chromosome regions 7p11.2 and 12q13-15. Although amplification is a well-known hallmark of glioblastoma genetics the function of most amplified genes in glioblastoma biology is not understood. Previously, we cloned Ku...

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Autores principales: FISCHER, ULRIKE, RHEINHEIMER, STEFANIE, KREMPLER, ANDREA, LÖBRICH, MARKUS, MEESE, ECKART
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742159/
https://www.ncbi.nlm.nih.gov/pubmed/23670597
http://dx.doi.org/10.3892/ijo.2013.1937
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author FISCHER, ULRIKE
RHEINHEIMER, STEFANIE
KREMPLER, ANDREA
LÖBRICH, MARKUS
MEESE, ECKART
author_facet FISCHER, ULRIKE
RHEINHEIMER, STEFANIE
KREMPLER, ANDREA
LÖBRICH, MARKUS
MEESE, ECKART
author_sort FISCHER, ULRIKE
collection PubMed
description Human glioblastomas are characterized by frequent DNA amplifications most often at chromosome regions 7p11.2 and 12q13-15. Although amplification is a well-known hallmark of glioblastoma genetics the function of most amplified genes in glioblastoma biology is not understood. Previously, we cloned Ku70-binding protein 3 (KUB3) from the amplified domain at 12q13-15. Here, we report that glioblastoma cell cultures with endogenous KUB3 gene amplification and with elevated KUB3 protein expression show an efficient double-strand break (DSB) repair after being irradiated with 1 Gy. A significantly less efficient DSB repair was found in glioma cell cultures without KUB3 amplification and expression. Furthermore, we found that a siRNA-mediated reduction of the endogenous KUB3 expression in glioblastoma cells resulted in a reduction of the repair efficiency. HeLa cells transfected with KUB3 showed an increased DSB repair in comparison to untreated HeLa cells. In addition, KUB3 seems to influence DSB efficiency via the DNA-PK-dependent repair pathway as shown by simultaneous inhibition of KUB3 and DNA-PK. The data provide the first evidence for a link between the level of KUB3 amplification and expression in glioma and DSB repair efficiency.
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spelling pubmed-37421592013-08-14 Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation FISCHER, ULRIKE RHEINHEIMER, STEFANIE KREMPLER, ANDREA LÖBRICH, MARKUS MEESE, ECKART Int J Oncol Articles Human glioblastomas are characterized by frequent DNA amplifications most often at chromosome regions 7p11.2 and 12q13-15. Although amplification is a well-known hallmark of glioblastoma genetics the function of most amplified genes in glioblastoma biology is not understood. Previously, we cloned Ku70-binding protein 3 (KUB3) from the amplified domain at 12q13-15. Here, we report that glioblastoma cell cultures with endogenous KUB3 gene amplification and with elevated KUB3 protein expression show an efficient double-strand break (DSB) repair after being irradiated with 1 Gy. A significantly less efficient DSB repair was found in glioma cell cultures without KUB3 amplification and expression. Furthermore, we found that a siRNA-mediated reduction of the endogenous KUB3 expression in glioblastoma cells resulted in a reduction of the repair efficiency. HeLa cells transfected with KUB3 showed an increased DSB repair in comparison to untreated HeLa cells. In addition, KUB3 seems to influence DSB efficiency via the DNA-PK-dependent repair pathway as shown by simultaneous inhibition of KUB3 and DNA-PK. The data provide the first evidence for a link between the level of KUB3 amplification and expression in glioma and DSB repair efficiency. D.A. Spandidos 2013-05-13 /pmc/articles/PMC3742159/ /pubmed/23670597 http://dx.doi.org/10.3892/ijo.2013.1937 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
FISCHER, ULRIKE
RHEINHEIMER, STEFANIE
KREMPLER, ANDREA
LÖBRICH, MARKUS
MEESE, ECKART
Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title_full Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title_fullStr Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title_full_unstemmed Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title_short Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
title_sort glioma-amplified sequence kub3 influences double-strand break repair after ionizing radiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742159/
https://www.ncbi.nlm.nih.gov/pubmed/23670597
http://dx.doi.org/10.3892/ijo.2013.1937
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