Dynamics of the DYNLL1/MRE11 complex regulates DNA end resection and recruitment of the Shieldin complex to DSBs
ABSTRACT Extent and efficacy of DNA end resection at DNA double strand break (DSB)s determines the choice of repair pathway. Here we describe how the 53BP1 associated protein DYNLL1 works in tandem with Shieldin and the CST 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 the G1 cells. Shieldin localization to DSBs is dependent 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 re-sensitized 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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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Rui [VerfasserIn] |
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| doi: |
10.1101/2023.03.27.534416 |
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| PPN (Katalog-ID): |
XBI039096912 |
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| 245 | 1 | 0 | |a Dynamics of the DYNLL1/MRE11 complex regulates DNA end resection and recruitment of the Shieldin complex to DSBs |
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| 520 | |a ABSTRACT Extent and efficacy of DNA end resection at DNA double strand break (DSB)s determines the choice of repair pathway. Here we describe how the 53BP1 associated protein DYNLL1 works in tandem with Shieldin and the CST 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 the G1 cells. Shieldin localization to DSBs is dependent 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 re-sensitized 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 Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Swift, Michelle L. |e verfasserin |0 (orcid)0000-0003-3645-1308 |4 aut | |
| 700 | 1 | |a Syed, Aleem |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Kaimeng |e verfasserin |4 aut | |
| 700 | 1 | |a Moreau, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Tainer, John A. |e verfasserin |4 aut | |
| 700 | 1 | |a Konstantinopoulos, Panagiotis A. |e verfasserin |4 aut | |
| 700 | 1 | |a D’Andrea, Alan D. |e verfasserin |0 (orcid)0000-0001-6168-6294 |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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