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The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells

Averbeck, Nicole B. ; Barent, Carina ; Jakob, Burkhard ; Syzonenko, Tatyana ; Durante, Marco ; Taucher-Scholz, Gisela (2022)
The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells.
In: Cells, 2022, 11 (16)
doi: 10.26083/tuprints-00022312
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells
Language: English
Date: 31 October 2022
Place of Publication: Darmstadt
Year of primary publication: 2022
Publisher: MDPI
Journal or Publication Title: Cells
Volume of the journal: 11
Issue Number: 16
Collation: 19 Seiten
DOI: 10.26083/tuprints-00022312
Corresponding Links:
Origin: Secondary publication DeepGreen
Abstract:

DNA double-strand breaks (DSBs) represent the molecular origin of ionizing-radiation inflicted biological effects. An increase in the ionization density causes more complex, clustered DSBs that can be processed by resection also in G1 phase, where repair of resected DSBs is considered erroneous and may contribute to the increased biological effectiveness of heavy ions in radiotherapy. To investigate the resection regulation of complex DSBs, we exposed G1 cells depleted for different candidate factors to heavy ions or α-particle radiation. Immunofluorescence microscopy was used to monitor the resection marker RPA, the DSB marker γH2AX and the cell-cycle markers CENP-F and geminin. The Fucci system allowed to select G1 cells, cell survival was measured by clonogenic assay. We show that in G1 phase the ubiquitin ligase RNF138 functions in resection regulation. RNF138 ubiquitinates the resection factor CtIP in a radiation-dependent manner to allow its DSB recruitment in G1 cells. At complex DSBs, RNF138′s participation becomes more relevant, consistent with the observation that also resection is more frequent at these DSBs. Furthermore, deficiency of RNF138 affects both DSB repair and cell survival upon induction of complex DSBs. We conclude that RNF138 is a regulator of resection that is influenced by DSB complexity and can affect the quality of DSB repair in G1 cells.

Uncontrolled Keywords: DNA double-strand break (DSB), complex DSBs, DSB resection, ubiquitination, RNF138, CtIP, heavy ions, radiotherapy
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-223127
Additional Information:

This article belongs to the Special Issue Double-Strand DNA Break Repair and Human Disease II

Classification DDC: 500 Science and mathematics > 530 Physics
500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
05 Department of Physics > Institute for Condensed Matter Physics
Date Deposited: 31 Oct 2022 14:26
Last Modified: 14 Nov 2023 19:05
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/22312
PPN: 501072624
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