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
Artikel, Zweitveröffentlichung, Verlagsversion
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Averbeck, Nicole B. ; Barent, Carina ; Jakob, Burkhard ; Syzonenko, Tatyana ; Durante, Marco ; Taucher-Scholz, Gisela |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Cells |
| Jahrgang/Volume einer Zeitschrift: | 11 |
| (Heft-)Nummer: | 16 |
| Kollation: | 19 Seiten |
| DOI: | 10.26083/tuprints-00022312 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22312 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (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. |
| Freie Schlagworte: | DNA double-strand break (DSB), complex DSBs, DSB resection, ubiquitination, RNF138, CtIP, heavy ions, radiotherapy |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-223127 |
| Zusätzliche Informationen: | This article belongs to the Special Issue Double-Strand DNA Break Repair and Human Disease II |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 530 Physik 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair 05 Fachbereich Physik 05 Fachbereich Physik > Institut für Physik Kondensierter Materie (IPKM) |
| Hinterlegungsdatum: | 31 Okt 2022 14:26 |
| Letzte Änderung: | 01 Nov 2022 08:38 |
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