Iho1-KO Mouse

Iho1, also known as CCDC36, is an essential protein for meiotic DNA double-strand break (DSB) formation. It is evolutionarily conserved from fungi to mammals [5]. In meiosis, DSBs are crucial for homologous chromosome pairing, synapsis, and genetic diversity. Iho1 is part of the regulatory machinery for DSB formation, which is a key process in the meiotic recombination pathway [1-8].

In mouse models, Iho1 has been shown to have multiple important functions. Iho1 forms axial platforms with HORMAD1, a chromosomal axis component, and this interaction is essential for the efficient biogenesis of DSB-machinery clusters. Without the Iho1-HORMAD1 interaction, residual DSBs rely on ANKRD31 [1,4]. Iho1 is also phosphorylated, and its phosphorylation and the formation of axial platforms are regulated by DBF4-dependent kinase (DDK) [1]. Moreover, Iho1 directly interacts with the PH domain of REC114, suggesting the existence of a ternary Iho1-REC114-MEI4 complex that controls DSB formation [2]. Additionally, DSBs can restrict the DSB machinery through multiple pathways related to Iho1, such as by activating DDR kinases that can trigger Iho1 depletion [3].

In conclusion, Iho1 is vital for meiotic DSB formation. Mouse models, especially those with gene knockout or conditional knockout of Iho1, have revealed its role in ensuring sufficient DSBs for homologous chromosome pairing and in the spatiotemporal control of the DSB machinery. Understanding Iho1's function contributes to our knowledge of meiotic processes and potential implications for fertility-related issues.

References:

1. Dereli, Ihsan, Telychko, Vladyslav, Papanikos, Frantzeskos, Keeney, Scott, Tóth, Attila. 2024. Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes. In Nature communications, 15, 2941. doi:10.1038/s41467-024-47020-1. https://pubmed.ncbi.nlm.nih.gov/38580643/

2. Laroussi, Hamida, Juarez-Martinez, Ariadna B, Le Roy, Aline, de Massy, Bernard, Kadlec, Jan. 2023. Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation. In The EMBO journal, 42, e113866. doi:10.15252/embj.2023113866. https://pubmed.ncbi.nlm.nih.gov/37431931/

3. Dereli, Ihsan, Stanzione, Marcello, Olmeda, Fabrizio, Rulands, Steffen, Tóth, Attila. . Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice. In Nucleic acids research, 49, 2609-2628. doi:10.1093/nar/gkab082. https://pubmed.ncbi.nlm.nih.gov/33619545/

4. Dereli, Ihsan, Telychko, Vladyslav, Papanikos, Frantzeskos, Keeney, Scott, Tóth, Attila. 2023. Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.11.27.568863. https://pubmed.ncbi.nlm.nih.gov/38077023/

5. Tessé, Sophie, Bourbon, Henri-Marc, Debuchy, Robert, Zickler, Denise, Espagne, Eric. 2017. Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction. In Genes & development, 31, 1880-1893. doi:10.1101/gad.304543.117. https://pubmed.ncbi.nlm.nih.gov/29021238/