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The Chromatin Architectural Protein CTCF Is Critical for Cell Survival upon Irradiation-Induced DNA Damage

Mamberti, Stefania ; Pabba, Maruthi Kumar ; Rapp, Alexander ; Cardoso, M. Cristina ; Scholz, Michael (2022):
The Chromatin Architectural Protein CTCF Is Critical for Cell Survival upon Irradiation-Induced DNA Damage. (Publisher's Version)
In: International Journal of Molecular Sciences, 23 (7), MDPI, e-ISSN 1422-0067,
DOI: 10.26083/tuprints-00021462,
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Item Type: Article
Origin: Secondary publication via sponsored Golden Open Access
Status: Publisher's Version
Title: The Chromatin Architectural Protein CTCF Is Critical for Cell Survival upon Irradiation-Induced DNA Damage
Language: English
Abstract:

CTCF is a nuclear protein initially discovered for its role in enhancer-promoter insulation. It has been shown to play a role in genome architecture and in fact, its DNA binding sites are enriched at the borders of chromatin domains. Recently, we showed that depletion of CTCF impairs the DNA damage response to ionizing radiation. To investigate the relationship between chromatin domains and DNA damage repair, we present here clonogenic survival assays in different cell lines upon CTCF knockdown and ionizing irradiation. The application of a wide range of ionizing irradiation doses (0–10 Gy) allowed us to investigate the survival response through a biophysical model that accounts for the double-strand breaks’ probability distribution onto chromatin domains. We demonstrate that the radiosensitivity of different cell lines is increased upon lowering the amount of the architectural protein. Our model shows that the deficiency in the DNA repair ability is related to the changes in the size of chromatin domains that occur when different amounts of CTCF are present in the nucleus.

Journal or Publication Title: International Journal of Molecular Sciences
Volume of the journal: 23
Issue Number: 7
Place of Publication: Darmstadt
Publisher: MDPI
Collation: 28 Seiten
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 02 Jun 2022 11:10
Last Modified: 04 Sep 2022 18:01
DOI: 10.26083/tuprints-00021462
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-214628
Additional Information:

Keywords: cancer; chromatin architecture; chromatin domain; clonogenic survival; CTCF; DNA damage response; DNA repair; ionizing radiation; radiosensitivity; biophysical modeling

URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/21462
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