Kakarougkas, Andreas ; Ismail, Amani ; Klement, Karolin ; Goodarzi, Aaron A. ; Conrad, Sandro ; Freire, Raimundo ; Shibata, Atsushi ; Löbrich, Markus ; Jeggo, Penny A. (2022)
Opposing roles for 53BP1 during homologous recombination.
In: Nucleic Acids Research, 2013, 41 (21)
doi: 10.26083/tuprints-00019031
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
Although DNA non-homologous end-joining repairs most DNA double-strand breaks (DSBs) in G2 phase, late repairing DSBs undergo resection and repair by homologous recombination (HR). Based on parallels to the situation in G1 cells, previous work has suggested that DSBs that undergo repair by HR predominantly localize to regions of heterochromatin (HC). By using H3K9me3 and H4K20me3 to identify HC regions, we substantiate and extend previous evidence, suggesting that HC-DSBs undergo repair by HR. Next, we examine roles for 53BP1 and BRCA1 in this process. Previous studies have shown that 53BP1 is pro-non-homologous end-joining and anti-HR. Surprisingly, we demonstrate that in G2 phase, 53BP1 is required for HR at HC-DSBs with its role being to promote phosphorylated KAP-1 foci formation. BRCA1, in contrast, is dispensable for pKAP-1 foci formation but relieves the barrier caused by 53BP1. As 53BP1 is retained at irradiation-induced foci during HR, we propose that BRCA1 promotes displacement but retention of 53BP1 to allow resection and any necessary HC modifications to complete HR. In contrast to this role for 53BP1 in HR in G2 phase, we show that it is dispensable for HR in S phase, where HC regions are likely relaxed during replication.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Kakarougkas, Andreas ; Ismail, Amani ; Klement, Karolin ; Goodarzi, Aaron A. ; Conrad, Sandro ; Freire, Raimundo ; Shibata, Atsushi ; Löbrich, Markus ; Jeggo, Penny A. |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Opposing roles for 53BP1 during homologous recombination |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Publikationsdatum der Erstveröffentlichung: | 2013 |
| Verlag: | Oxford University Press |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nucleic Acids Research |
| Jahrgang/Volume einer Zeitschrift: | 41 |
| (Heft-)Nummer: | 21 |
| DOI: | 10.26083/tuprints-00019031 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/19031 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (Abstract): | Although DNA non-homologous end-joining repairs most DNA double-strand breaks (DSBs) in G2 phase, late repairing DSBs undergo resection and repair by homologous recombination (HR). Based on parallels to the situation in G1 cells, previous work has suggested that DSBs that undergo repair by HR predominantly localize to regions of heterochromatin (HC). By using H3K9me3 and H4K20me3 to identify HC regions, we substantiate and extend previous evidence, suggesting that HC-DSBs undergo repair by HR. Next, we examine roles for 53BP1 and BRCA1 in this process. Previous studies have shown that 53BP1 is pro-non-homologous end-joining and anti-HR. Surprisingly, we demonstrate that in G2 phase, 53BP1 is required for HR at HC-DSBs with its role being to promote phosphorylated KAP-1 foci formation. BRCA1, in contrast, is dispensable for pKAP-1 foci formation but relieves the barrier caused by 53BP1. As 53BP1 is retained at irradiation-induced foci during HR, we propose that BRCA1 promotes displacement but retention of 53BP1 to allow resection and any necessary HC modifications to complete HR. In contrast to this role for 53BP1 in HR in G2 phase, we show that it is dispensable for HR in S phase, where HC regions are likely relaxed during replication. |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-190319 |
| Zusätzliche Informationen: | Supplementary Data: https://t1p.de/rsxz |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 23 Mär 2022 12:37 |
| Letzte Änderung: | 24 Mär 2022 09:50 |
| PPN: | |
| Export: | |
| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
- Opposing roles for 53BP1 during homologous recombination. (deposited 23 Mär 2022 12:37) [Gegenwärtig angezeigt]
 |
Frage zum Eintrag |
Optionen (nur für Redakteure)
 |
Redaktionelle Details anzeigen |
Drucken
Impressum