RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions
| Autor: | Alexander V. Mazin, Nadish Goyal, Olga M. Mazina, Matthew J. Rossi, Bruce E. Clurman, Yong Chi, Robert L. Moritz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Consensus site DNA Repair DNA repair Science General Physics and Astronomy Spodoptera DNA-binding protein General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ATP hydrolysis Holliday junction Sf9 Cells Animals Humans Amino Acid Sequence Binding site Phosphorylation lcsh:Science Adenosine Triphosphatases Recombination Genetic DNA Cruciform Multidisciplinary Binding Sites Sequence Homology Amino Acid Chemistry Hydrolysis fungi DNA Helicases Nuclear Proteins General Chemistry Branch migration Cell biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) 030104 developmental biology Nucleic Acid Conformation lcsh:Q Protein Multimerization 030217 neurology & neurosurgery DNA |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | In eukaryotes, RAD54 catalyzes branch migration (BM) of Holliday junctions, a basic process during DNA repair, replication, and recombination. RAD54 also stimulates RAD51 recombinase and has other activities. Here, we investigate the structural determinants for different RAD54 activities. We find that the RAD54 N-terminal domain (NTD) is responsible for initiation of BM through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. Furthermore, we find that the RAD54 oligomeric state can be controlled by NTD phosphorylation at S49, a CDK2 consensus site, which inhibits RAD54 oligomerization and, consequently, BM. Importantly, the effect of phosphorylation on RAD54 oligomerization is specific for BM, as it does not affect stimulation of RAD51 recombinase by RAD54. Thus, the transition of the oligomeric states provides an important control of the biological functions of RAD54 and, likely, other multifunctional proteins. RAD54 stimulates activity of the RAD51 recombinase and catalyzes branch migration of Holliday junctions during DNA repair and recombination. Here the authors show that the N-terminal domain of RAD54 mediates RAD54 oligomerization to promote branch migration, and is the target of phosphorylation that inhibits oligomerization and branch migration but not RAD51 stimulation. |
| Databáze: | OpenAIRE |
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