| Autor: |
Laroussi, Hamida, Juarez‐Martinez, Ariadna B, Le Roy, Aline, Boeri Erba, Elisabetta, Gabel, Frank, de Massy, Bernard, Kadlec, Jan |
| Předmět: |
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| Zdroj: |
EMBO Journal; Aug2023, Vol. 42 Issue 16, p1-17, 17p |
| Abstrakt: |
Meiotic recombination is initiated by the formation of DNA double‐strand breaks (DSBs), essential for fertility and genetic diversity. In the mouse, DSBs are formed by the catalytic TOPOVIL complex consisting of SPO11 and TOPOVIBL. To preserve genome integrity, the activity of the TOPOVIL complex is finely controlled by several meiotic factors including REC114, MEI4, and IHO1, but the underlying mechanism is poorly understood. Here, we report that mouse REC114 forms homodimers, that it associates with MEI4 as a 2:1 heterotrimer that further dimerizes, and that IHO1 forms coiled‐coil‐based tetramers. Using AlphaFold2 modeling combined with biochemical characterization, we uncovered the molecular details of these assemblies. Finally, we show that IHO1 directly interacts with the PH domain of REC114 by recognizing the same surface as TOPOVIBL and another meiotic factor ANKRD31. These results provide strong evidence for the existence of a ternary IHO1‐REC114‐MEI4 complex and suggest that REC114 could act as a potential regulatory platform mediating mutually exclusive interactions with several partners. Synopsis: REC114, MEI4, and IHO1 are established regulators of DNA double‐strand breaks during meiotic recombination. This study reveals that these three factors form a stable complex and provides structural and biophysical insights into its architecture.REC114 dimerizes via its C terminus and interacts with the N terminus of MEI4 to form complexes with 2:1 and 4:2 stoichiometry.IHO1 forms homotetramers via a parallel four‐stranded coiled‐coil.IHO1 and REC114‐MEI4 form a stable complex requiring a highly conserved N terminus of IHO1 and the Pleckstrin homology domain of REC114.REC114 interaction with IHO1 is mutually exclusive with its binding to ANKRD31 and TOPOVIBL. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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