RADX controls RAD51 filament dynamics to regulate replication fork stability
| Autor: | Florian Morati, Madison B. Adolph, Chaoyou Xue, Eric C. Greene, Swati Balakrishnan, Walter J. Chazin, Taha M. Mohamed, David Cortez, Mauro Modesti |
|---|---|
| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Replication fork reversal
Genome instability DNA Replication DNA repair [SDV]Life Sciences [q-bio] genetic processes Green Fluorescent Proteins RAD51 DNA Single-Stranded Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate ATP hydrolysis Genes Reporter Cell Line Tumor Humans Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology BRCA2 Protein 0303 health sciences Binding protein Hydrolysis DNA replication RNA-Binding Proteins Cell Biology DNA Fibroblasts Single Molecule Imaging Cell biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Luminescent Proteins HEK293 Cells chemistry Gene Expression Regulation health occupations Rad51 Recombinase biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Molecular Cell Molecular Cell, Elsevier, 2021, 81 (5), pp.1074-1083.e5. ⟨10.1016/j.molcel.2020.12.036⟩ Mol Cell Molecular Cell, 2021, 81 (5), pp.1074-1083.e5. ⟨10.1016/j.molcel.2020.12.036⟩ |
| ISSN: | 1097-2765 1097-4164 |
| DOI: | 10.1016/j.molcel.2020.12.036⟩ |
| Popis: | The RAD51 recombinase forms nucleoprotein filaments to promote double-strand break repair, replication fork reversal, and fork stabilization. The stability of these filaments is highly regulated since both too little and too much RAD51 activity can cause genome instability. RADX is a single-strand DNA (ssDNA) binding protein that regulates DNA replication. Here we define its mechanism of action. We find that RADX inhibits RAD51 strand exchange and D-loop formation activities. RADX directly and selectively interacts with ATP-bound RAD51, stimulates ATP hydrolysis, and destabilizes RAD51 nucleofilaments. The RADX interaction with RAD51, in addition to its ssDNA binding capability, is required to maintain replication fork elongation rates and fork stability. Furthermore, BRCA2 can overcome the RADX-dependent RAD51 inhibition. Thus, RADX functions in opposition to BRCA2 in regulating RAD51 nucleofilament stability to ensure the right level of RAD51 function during DNA replication. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|