| Title: |
Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection |
| Authors: |
Ferretti, Lorenza P; Himmels, Sarah-Felicitas; Trenner, Anika; Walker, Christina; von Aesch, Christine; Eggenschwiler, Aline; Murina, Olga; Enchev, Radoslav I; Peter, Matthias; Freire, Raimundo; Porro, Antonio; Sartori, Alessandro A |
| Source: |
Ferretti, Lorenza P; Himmels, Sarah-Felicitas; Trenner, Anika; Walker, Christina; von Aesch, Christine; Eggenschwiler, Aline; Murina, Olga; Enchev, Radoslav I; Peter, Matthias; Freire, Raimundo; Porro, Antonio; Sartori, Alessandro A (2016). Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection. Nature Communications, 7:12628. |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2016 |
| Collection: |
University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| Subject Terms: |
Institute of Molecular Cancer Research; 570 Life sciences; biology; 610 Medicine & health |
| Description: |
Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of DNA-end resection, CtIP function is tightly controlled by multiple protein-protein interactions and post-translational modifications. Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A tripeptide motif (FRY) conserved across vertebrate CtIP proteins is essential for KLHL15-binding; its mutation blocks KLHL15-dependent CtIP ubiquitination and degradation. Consequently, DNA-end resection is strongly attenuated in cells overexpressing KLHL15 but amplified in cells either expressing a CtIP-FRY mutant or lacking KLHL15, thus impacting the balance between HR and NHEJ. Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://www.zora.uzh.ch/id/eprint/126354/1/ncomms12628.pdf; info:pmid/27561354; urn:issn:2041-1723 |
| DOI: |
10.1038/ncomms12628 |
| Availability: |
https://www.zora.uzh.ch/id/eprint/126354/; https://www.zora.uzh.ch/id/eprint/126354/1/ncomms12628.pdf; https://doi.org/10.1038/ncomms12628 |
| Rights: |
info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.DD2E36AD |
| Database: |
BASE |