5.9
CiteScore
5.9
Impact Factor
Volume 47 Issue 8
Aug.  2020
Turn off MathJax
Article Contents

The novel male meiosis recombination regulator coordinates the progression of meiosis prophase I

doi: 10.1016/j.jgg.2020.08.001
More Information
  • Corresponding author: E-mail address: miaoli@hku.hk (Miao Li); E-mail address: kliugc@hku.hk (Kui Liu)
  • Publish Date: 2020-08-25
  • Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms. In this study, we have independently identified a novel meiosis protein male meiosis recombination regulator (MAMERR)/4930432K21Rik and showed that it is indispensable for meiosis prophase I progression in male mice. Using super-resolution structured illumination microscopy, we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 complex. We generated a Mamerr-deficient mouse model by deleting exons 3–6 and found that most of Mamerr spermatocytes were arrested at pachynema and failed to progress to diplonema, although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body formation. Further mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2–binding protein in Mamerr spermatocytes was only mildly impaired with a partial reduction in double-strand break repair, whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerr spermatocytes. We propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes, and in the absence of MAMERR, the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.
  • These authors contributed equally to this work.
  • loading
  • [1]
    Baarends, W.M., Wassenaar, E., van der Laan, R., Hoogerbrugge, J., Sleddens-Linkels, E., Hoeijmakers, J.H., de Boer, P., Grootegoed, J.A., 2005. Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Mol Cell Biol. 25, 1041-1053.
    [2]
    Baker, S.M., Plug, A.W., Prolla, T.A., Bronner, C.E., Harris, A.C., Yao, X., Christie, D.M., Monell, C., Arnheim, N., Bradley, A., Ashley, T., Liskay, R.M., 1996. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat. Genet. 13, 336-342.
    [3]
    Baudat, F., Buard, J., Grey, C., Fledel-Alon, A., Ober, C., Przeworski, M., Coop, G., De Massy, B., 2010. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327, 836-840.
    [4]
    Bose, R., Manku, G., Culty, M., Wing, S.S., 2014. Ubiquitin-proteasome system in spermatogenesis. Adv Exp Med Biol. 759, 181-213.
    [5]
    Brandsma, I., Sato, K., van Rossum-Fikkert, S.E., van Vliet, N., Sleddens, E., Reuter, M., Odijk, H., van den Tempel, N., Dekkers, D.H.W., Bezstarosti, K., Demmers, J.A.A., Maas, A., Lebbink, J., Wyman, C., Essers, J., van Gent, D.C., Baarends, W.M., Knipscheer, P., Kanaar, R., Zelensky, A.N., 2019. HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis. Cell Rep. 27, 3790-3798.e3797.
    [6]
    Cloud, V., Chan, Y.L., Grubb, J., Budke, B., Bishop, D.K., 2012. Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis. Science 337, 1222-1225.
    [7]
    Edelmann, W., Cohen, P.E., Kane, M., Lau, K., Morrow, B., Bennett, S., Umar, A., Kunkel, T., Cattoretti, G., Chaganti, R., Pollard, J.W., Kolodner, R.D., Kucherlapati, R., 1996. Meiotic pachytene arrest in MLH1-deficient mice. Cell 85, 1125-1134.
    [8]
    Enguita-Marruedo, A., Sleddens-Linkels, E., Ooms, M., de Geus, V., Wilke, M., Blom, E., Dohle, G.R., Looijenga, L.H.J., van Cappellen, W., Baart, E.B., Baarends, W.M., 2019. Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men. Fertil Steril. 112, 1059-1070 e1053.
    [9]
    Gan, H., Wen, L., Liao, S., Lin, X., Ma, T., Liu, J., Song, C.X., Wang, M., He, C., Han, C., Tang, F., 2013. Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis. Nat. Commun. 4, 1995.
    [10]
    Handel, M.A., Schimenti, J.C., 2010. Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet. 11, 124-136.
    [11]
    Hasegawa, K., Sin, H.S., Maezawa, S., Broering, T.J., Kartashov, A.V., Alavattam, K.G., Ichijima, Y., Zhang, F., Bacon, W.C., Greis, K.D., Andreassen, P.R., Barski, A., Namekawa, S.H., 2015. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 32, 574-588.
    [12]
    Hays, E., Majchrzak, N., Daniel, V., Ferguson, Z., Brown, S., Hathorne, K., La Salle, S., 2017. Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells. Andrology 5, 299-312.
    [13]
    Hicke, L., 2001. Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol. 2, 195-201.
    [14]
    Hirota, T., Blakeley, P., Sangrithi, M.N., Mahadevaiah, S.K., Encheva, V., Snijders, A.P., ElInati, E., Ojarikre, O.A., de Rooij, D.G., Niakan, K.K., Turner, J.M.A., 2018. SETDB1 Links the Meiotic DNA Damage Response to Sex Chromosome Silencing in Mice. Dev Cell. 47, 645-659 e646.
    [15]
    Ichijima, Y., Ichijima, M., Lou, Z., Nussenzweig, A., Camerini-Otero, R.D., Chen, J., Andreassen, P.R., Namekawa, S.H., 2011. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 25, 959-971.
    [16]
    Jensen, R.B., Carreira, A., Kowalczykowski, S.C., 2010. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 467, 678-683.
    [17]
    Keeney, S., Neale, M.J., 2006. Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation. Biochem Soc Trans. 34, 523-525.
    [18]
    Kornberg, R.D., 1974. Chromatin structure: a repeating unit of histones and DNA. Science 184, 868-871.
    [19]
    La Salle, S., Palmer, K., O'Brien, M., Schimenti, J.C., Eppig, J., Handel, M.A., 2012. Spata22, a novel vertebrate-specific gene, is required for meiotic progress in mouse germ cells. Biol Reprod. 86, 45.
    [20]
    Li, M., Huang, T., Li, M.J., Zhang, C.X., Yu, X.C., Yin, Y.Y., Liu, C., Wang, X., Feng, H.W., Zhang, T., Liu, M.F., Han, C.S., Lu, G., Li, W., Ma, J.L., Chen, Z.J., Liu, H.B., Liu, K., 2019. The histone modification reader ZCWPW1 is required for meiosis prophase I in male but not in female mice. Sci Adv. 5, eaax1101.
    [21]
    Liu, H., Huang, T., Li, M., Li, M., Zhang, C., Jiang, J., Yu, X., Yin, Y., Zhang, F., Lu, G., Luo, M.C., Zhang, L.R., Li, J., Liu, K., Chen, Z.J., 2019. SCRE serves as a unique synaptonemal complex fastener and is essential for progression of meiosis prophase I in mice. Nucleic Acids Res. 47, 5670-5683
    [22]
    Lu, L.-Y., Wu, J., Ye, L., Gavrilina, G.B., Saunders, T.L., Yu, X., 2010. RNF8-Dependent Histone Modifications Regulate Nucleosome Removal during Spermatogenesis. Dev Cell. 18, 371-384.
    [23]
    Lu, L.Y., Xiong, Y., Kuang, H., Korakavi, G., Yu, X., 2013. Regulation of the DNA damage response on male meiotic sex chromosomes. Nat. Commun. 4, 2105.
    [24]
    Luo, M., Yang, F., Leu, N.A., Landaiche, J., Handel, M.A., Benavente, R., La Salle, S., Wang, P.J., 2013. MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination. Nat. Commun. 4, 2788.
    [25]
    Luo, M., Zhou, J., Leu, N.A., Abreu, C.M., Wang, J., Anguera, M.C., de Rooij, D.G., Jasin, M., Wang, P.J., 2015. Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis. PLoS Genet. 11, e1004954.
    [26]
    Maezawa, S., Hasegawa, K., Alavattam, K.G., Funakoshi, M., Sato, T., Barski, A., Namekawa, S.H., 2018. SCML2 promotes heterochromatin organization in late spermatogenesis. J Cell Sci. 131.
    [27]
    Oh, E., Mark, K.G., Mocciaro, A., Watson, E.R., Prabu, J.R., Cha, D.D., Kampmann, M., Gamarra, N., Zhou, C.Y., Rape, M., 2020. Gene expression and cell identity controlled by anaphase-promoting complex. Nature 579, 136-140.
    [28]
    Peters, A.H., Plug, A.W., van Vugt, M.J., de Boer, P., 1997. A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res. 5, 66-68.
    [29]
    Qiao, H., Prasada Rao, H.B., Yang, Y., Fong, J.H., Cloutier, J.M., Deacon, D.C., Nagel, K.E., Swartz, R.K., Strong, E., Holloway, J.K., Cohen, P.E., Schimenti, J., Ward, J., Hunter, N., 2014. Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nat. Genet. 46, 194-199.
    [30]
    Rao, H.B., Qiao, H., Bhatt, S.K., Bailey, L.R., Tran, H.D., Bourne, S.L., Qiu, W., Deshpande, A., Sharma, A.N., Beebout, C.J., Pezza, R.J., Hunter, N., 2017. A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination. Science 355, 403-407.
    [31]
    Reynolds, A., Qiao, H., Yang, Y., Chen, J.K., Jackson, N., Biswas, K., Holloway, J.K., Baudat, F., de Massy, B., Wang, J., Hoog, C., Cohen, P.E., Hunter, N., 2013. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nat. Genet. 45, 269-278.
    [32]
    Ribeiro, J., Abby, E., Livera, G., Martini, E., 2016. RPA homologs and ssDNA processing during meiotic recombination. Chromosoma 125, 265-276.
    [33]
    Ryu, K.Y., Sinnar, S.A., Reinholdt, L.G., Vaccari, S., Hall, S., Garcia, M.A., Zaitseva, T.S., Bouley, D.M., Boekelheide, K., Handel, M.A., Conti, M., Kopito, R.R., 2008. The mouse polyubiquitin gene Ubb is essential for meiotic progression. Mol Cell Biol. 28, 1136-1146.
    [34]
    Shi, B., Xue, J., Yin, H., Guo, R., Luo, M., Ye, L., Shi, Q., Huang, X., Liu, M., Sha, J., Wang, P.J., 2019. Dual functions for the ssDNA-binding protein RPA in meiotic recombination. PLoS Genet. 15, e1007952.
    [35]
    Sinnar, S.A., Small, C.L., Evanoff, R.M., Reinholdt, L.G., Griswold, M.D., Kopito, R.R., Ryu, K.Y., 2011. Altered testicular gene expression patterns in mice lacking the polyubiquitin gene Ubb. Mol Reprod Dev. 78, 415-425.
    [36]
    Soh, Y.Q., Junker, J.P., Gill, M.E., Mueller, J.L., van Oudenaarden, A., Page, D.C., 2015. A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary. PLoS Genet. 11, e1005531.
    [37]
    Takemoto, K., Tani, N., Takada-Horisawa, Y., Fujimura, S., Tanno, N., Yamane, M., Okamura, K., Sugimoto, M., Araki, K., Ishiguro, K.I., 2020. Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination. Cell Rep. 31, 107686.
    [38]
    Thorslund, T., Esashi, F., West, S.C., 2007. Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1. EMBO J. 26, 2915-2922.
    [39]
    Turner, J.M., 2007. Meiotic sex chromosome inactivation. Development 134, 1823-1831.
    [40]
    Uckelmann, M., Sixma, T.K., 2017. Histone ubiquitination in the DNA damage response. DNA Repair 56, 92-101.
    [41]
    Wold, M.S., 1997. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu Rev Biochem. 66, 61-92.
    [42]
    Xu, Y., Greenberg, R.A., Schonbrunn, E., Wang, P.J., 2017. Meiosis-specific proteins MEIOB and SPATA22 cooperatively associate with the single-stranded DNA-binding replication protein A complex and DNA double-strand breaks. Biol Reprod. 96, 1096-1104.
    [43]
    Xu, Z., Song, Z., Li, G., Tu, H., Liu, W., Liu, Y., Wang, P., Wang, Y., Cui, X., Liu, C., Shang, Y., de Rooij, D.G., Gao, F., Li, W., 2016. H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation. Nucleic Acids Res. 44, 9681-9697.
    [44]
    Zhang, J., Gurusaran, M., Fujiwara, Y., Zhang, K., Echbarthi, M., Vorontsov, E., Guo, R., Pendlebury, D.F., Alam, I., Livera, G., Emmanuelle, M., Wang, P.J., Nandakumar, J., Davies, O.R., Shibuya, H., 2020. The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nat. Commun. 11, 2055.
    [45]
    Zickler, D., Kleckner, N., 1999. Meiotic chromosomes: integrating structure and function. Annu Rev Genet. 33, 603-754.
    [46]
    Zickler, D., Kleckner, N., 2015. Recombination, Pairing, and Synapsis of Homologs during Meiosis. Cold Spring Harb Perspect Biol. 7.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures (7)

    Article Metrics

    Article views (94) PDF downloads (5) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return