{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IHO1 functions as a key facilitator of programmed DNA double‐strand break (DSB) formation during meiosis by serving as an essential anchor for the assembly of pre‐DSB “recombinosomes.” In mouse meiocytes, IHO1 is recruited to the unsynapsed regions of the chromosome axis through its interaction with HORMAD1, thereby ensuring that SPO11 and its auxiliary proteins (including MEI4 and REC114) are efficiently assembled at sites where DSBs must occur to promote homolog pairing and subsequent crossover formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, IHO1 interacts with other factors such as CXXC1—a homolog of the yeast histone methyl reader Spp1—that likely bridge activated recombination hotspots with the chromosome axis, underscoring a conserved mechanism in linking local chromatin modifications to the DSB machinery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Axis-associated cohesin components, such as STAG3 and REC8, further promote the proper localization of IHO1 together with HORMAD1 and MEI4, thus contributing to the spatial regulation of SPO11 activity along the axes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Finally, dynamic regulation of IHO1, including its depletion from synapsed chromosome axes mediated by DNA damage response kinases like ATR, constitutes a negative feedback loop that restricts DSB numbers to appropriate levels during meiotic prophase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marcello Stanzione, Marek Baumann, Frantzeskos Papanikos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3417"}], "href": "https://doi.org/10.1038/ncb3417"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27723721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27723721"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yukiko Imai, Frédéric Baudat, Miguel Taillepierre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PRDM9 KRAB domain is required for meiosis and involved in protein interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chromosoma (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00412-017-0631-z"}], "href": "https://doi.org/10.1007/s00412-017-0631-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28527011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28527011"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tanmoy Bhattacharyya, Michael Walker, Natalie R Powers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prdm9 and Meiotic Cohesin Proteins Cooperatively Promote DNA Double-Strand Break Formation in Mammalian Spermatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2019.02.007"}], "href": "https://doi.org/10.1016/j.cub.2019.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30853435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30853435"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ihsan Dereli, Marcello Stanzione, Fabrizio Olmeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkab082"}], "href": "https://doi.org/10.1093/nar/gkab082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33619545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33619545"}]}]}]}