Dynamics of the DYNLL1-MRE11 complex regulate DNA end resection and recruitment of Shieldin to DSBs
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc..
The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by the loss of Shieldin proteins can be resensitized by the constitutive association of DYNLL1 with MRE11. These results define the temporal and functional dynamics of the 53BP1-centric DNA end resection factors in cells.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Nature structural & molecular biology - 30(2023), 10 vom: 11. Okt., Seite 1456-1467 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Swift, Michelle L [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 01.12.2023 published: Print-Electronic UpdateOf: bioRxiv. 2023 Mar 27;:. - PMID 37034578 Citation Status MEDLINE |
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| doi: |
10.1038/s41594-023-01074-9 |
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| funding: |
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| PPN (Katalog-ID): |
NLM361943571 |
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| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc. | ||
| 520 | |a The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by the loss of Shieldin proteins can be resensitized by the constitutive association of DYNLL1 with MRE11. These results define the temporal and functional dynamics of the 53BP1-centric DNA end resection factors in cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Moreau, Lisa A |e verfasserin |4 aut | |
| 700 | 1 | |a Tomasik, Bartłomiej |e verfasserin |4 aut | |
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| 700 | 1 | |a Konstantinopoulos, Panagiotis A |e verfasserin |4 aut | |
| 700 | 1 | |a D'Andrea, Alan D |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yizhou Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Chowdhury, Dipanjan |e verfasserin |4 aut | |
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