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Opposing roles for 53BP1 during homologous recombination

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. (Publisher's Version)
In: Nucleic Acids Research, 41 (21), pp. 9719-9731. Oxford University Press, ISSN 0305-1048, e-ISSN 1362-4962,
DOI: 10.26083/tuprints-00019031,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: Opposing roles for 53BP1 during homologous recombination
Language: English
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.

Journal or Publication Title: Nucleic Acids Research
Volume of the journal: 41
Issue Number: 21
Publisher: Oxford University Press
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 23 Mar 2022 12:37
Last Modified: 23 Mar 2022 12:37
DOI: 10.26083/tuprints-00019031
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-190319
Additional Information:

Supplementary Data: https://t1p.de/rsxz

URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19031
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