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

Fischer, Ulrike ; Rheinheimer, Stefanie ; Krempler, Andrea ; Löbrich, Markus ; Meese, Eckart (2021)
Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation.
In: International Journal of Oncology, 43 (1)
doi: 10.26083/tuprints-00019034
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: Glioma-amplified sequence KUB3 influences double-strand break repair after ionizing radiation
Language: English
Date: 2021
Place of Publication: Darmstadt
Publisher: Spandidos Publications
Journal or Publication Title: International Journal of Oncology
Volume of the journal: 43
Issue Number: 1
DOI: 10.26083/tuprints-00019034
Corresponding Links:
Origin: Secondary publication service

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.

Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-190343
Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 07 Sep 2021 12:12
Last Modified: 07 Aug 2023 10:52
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19034
PPN: 510358136
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