ArticleCell discovery2023
A novel recombination protein C12ORF40/REDIC1 is required for meiotic crossover formation.
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Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 11 citations in OpenAlex.
- Variants in ZZS Complex-Associated Genes TEX11 and M1AP Are Responsible for Male Infertility and Nonobstructive Azoospermia.Andrology · 2026Article
- XPF-like domain in human SHOC1 is required for crossover formation and protecting autosome from MSUC.Nucleic acids research · 2026Article
- SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis.Cell proliferation · 2026Article
- Homozygous C12orf40 variant contributes to severe oligoasthenoteratozoospermia and sperm sex chromosome aneuploidy.Journal of assisted reproduction and genetics · 2026Article
- Ufd2p promotes efficient crossover formation by destabilizing Top2p during meiosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pathogenic Variants in PET Complex Encoding GenesHuman mutation · 2026Article
- HEIP1 orchestrates pro-crossover protein activity during mammalian meiosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- mRNA-Seq of testis and liver tissues reveals a testis-specific gene and alternative splicing associated with hybrid male sterility in dzo.Journal of animal science · 2024Article
- HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
22 authors at 1 institution in 1 country.
Suixing Fan *Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.ORCID http://orcid.org/0000-0002-6133-9759
Yuewen Wang *Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Hanwei Jiang *Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Xiaohua JiangDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Jianteng ZhouDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Yuying JiaoDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Jingwei YeDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Zishuo XuDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Yue WangDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Xuefeng XieDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Huan ZhangDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Yang LiDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Wei LiuDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Xiangjun ZhangDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Hui MaDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Baolu ShiDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Yuanwei ZhangDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Muhammad ZubairDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Wasim ShahDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China.
Zhipeng XuInstitute of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. 289051238@qq.com.
Bo XuDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China. bio-xubo@163.com.
Qinghua ShiDivision of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui, China. qshi@ustc.edu.cn.ORCID http://orcid.org/0000-0003-1180-9799
University of Science and Technology of China · CN
Funding
National Natural Science Foundation of China (National Science Foundation of China) 31871514National Natural Science Foundation of China (National Science Foundation of China) 31890780National Natural Science Foundation of China (National Science Foundation of China) 31900398National Natural Science Foundation of China (National Science Foundation of China) 32061143006National Natural Science Foundation of China (National Science Foundation of China) 32100689National Natural Science Foundation of China (National Science Foundation of China) 82071709National Natural Science Foundation of China (National Science Foundation of China) U21A20204
Abstract
During meiosis, at least one crossover must occur per homologous chromosome pair to ensure normal progression of meiotic division and accurate chromosome segregation. However, the mechanism of crossover formation is not fully understood. Here, we report a novel recombination protein, C12ORF40/REDIC1, essential for meiotic crossover formation in mammals. A homozygous frameshift mutation in C12orf40 (c.232_233insTT, p.Met78Ilefs*2) was identified in two infertile men with meiotic arrest. Spread mouse spermatocyte fluorescence immunostaining showed that REDIC1 forms discrete foci between the paired regions of homologous chromosomes depending on strand invasion and colocalizes with MSH4 and later with MLH1 at the crossover sites. Redic1 knock-in (KI) mice homozygous for mutation c.232_233insTT are infertile in both sexes due to insufficient crossovers and consequent meiotic arrest, which is also observed in our patients. The foci of MSH4 and TEX11, markers of recombination intermediates, are significantly reduced numerically in the spermatocytes of Redic1 KI mice. More importantly, our biochemical results show that the N-terminus of REDIC1 binds branched DNAs present in recombination intermediates, while the identified mutation impairs this interaction. Thus, our findings reveal a crucial role for C12ORF40/REDIC1 in meiotic crossover formation by stabilizing the recombination intermediates, providing prospective molecular targets for the clinical diagnosis and therapy of infertility.
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