{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEIOB is a meiosis‐specific protein that contains an OB domain homologous to one of the OB folds of RPA1 and exhibits single‐strand DNA binding with 3′–5′ exonuclease activity. It forms a complex with RPA and its partner SPATA22, localizing to distinct foci along meiotic chromosomes where it facilitates the repair of programmed DNA double‐strand breaks, promotes homologous chromosome synapsis, and ensures proper stabilization of recombinase foci (RAD51 and DMC1) necessary for successful homology search and exchange."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations have revealed that MEIOB function is tightly regulated in a dosage‐dependent manner. Specific missense mutations and small deletions (for example, affecting residues such as asparagine 64 and serine 67) render the protein unstable through self‑aggregation and reduced half‑life, resulting in impaired crossover formation during late meiotic recombination. In addition, live cell imaging studies demonstrate that the OB domain of MEIOB contains a concealed nuclear localization signal (NLS) that is exposed only upon interaction with SPATA22—a necessary step for its nuclear import and subsequent participation in DNA repair. Moreover, MEIOB along with SPATA22 appears to modulate the condensation of RPA‐coated ssDNA, highlighting a synergistic interplay during homologous recombination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe clinical significance of MEIOB is underscored by its association with human infertility. Disruption of MEIOB—whether by deleterious mutations identified through whole‐exome sequencing or through other genetic variants—leads to defective double‐strand break repair and impaired homologous chromosome synapsis, resulting in meiotic arrest and infertility in both sexes. These findings are supported by analyses linking MEIOB defects to conditions such as primary ovarian insufficiency and azoospermia, while additional studies have even highlighted its aberrant expression as a cancer‑testis antigen in triple‑negative breast cancers, suggesting potential roles beyond gametogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benoit Souquet, Emilie Abby, Roxane Hervé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MEIOB targets single-strand DNA and is necessary for meiotic recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003784"}], "href": "https://doi.org/10.1371/journal.pgen.1003784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24068956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24068956"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mengcheng Luo, Fang Yang, N Adrian Leu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3788"}], "href": "https://doi.org/10.1038/ncomms3788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24240703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24240703"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui Guo, Yang Xu, N Adrian Leu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkaa1016"}], "href": "https://doi.org/10.1093/nar/gkaa1016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33166385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33166385"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jonathan Ribeiro, Pauline Dupaigne, Cynthia Petrillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The meiosis-specific MEIOB-SPATA22 complex cooperates with RPA to form a compacted mixed MEIOB/SPATA22/RPA/ssDNA complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2021.103097"}], "href": "https://doi.org/10.1016/j.dnarep.2021.103097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33812231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33812231"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yating Xu, Zhen Chen, Panfeng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear localization of human MEIOB requires its NLS in the OB domain and interaction with SPATA22."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3724/abbs.2022156"}], "href": "https://doi.org/10.3724/abbs.2022156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36331299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36331299"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Moran Gershoni, Ron Hauser, Shimi Barda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dez016"}], "href": "https://doi.org/10.1093/humrep/dez016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30838384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30838384"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sandrine Caburet, Anne-Laure Todeschini, Cynthia Petrillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2019.03.075"}], "href": "https://doi.org/10.1016/j.ebiom.2019.03.075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31000419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31000419"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yayun Gu, Cheng Wang, Rongxuan Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cancer-testis gene, "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MEIOB,"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.20892/j.issn.2095-3941.2020.0071"}], "href": "https://doi.org/10.20892/j.issn.2095-3941.2020.0071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33628586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33628586"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yufan Wu, Yang Li, Ghulam Murtaza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing of consanguineous families with infertile men and women identifies homologous mutations in SPATA22 and MEIOB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deab185"}], "href": "https://doi.org/10.1093/humrep/deab185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34392356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34392356"}]}]}]}