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Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

机译：确保小鼠伪变性区域中的减数分裂DNA断裂形成

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摘要

In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination.Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.
机译：在小鼠中，性染色体的伪变透明染色体区域经历了动态结构重排，以促进高速率的DNA双链断裂，并确保大多数Eutherian哺乳动物的男性中的染色体染色体仅共享伪染色体区域的小型末端区段（PAR），其中必须发生双链断裂（DSB），用于正确的减数分裂偏析（1,2）。细胞如何确保在PAR中发生重组是未知的。在这里，我们介绍了PAR的动态超微结构，并识别控制雄性小鼠基因组中的DSB形成的Par最热门段的CIS-和杂物作用因子。在中置地形成之前，促进分析中的多种DSB促进因子超法，其染色体轴长细长，姐妹染色体分开。这些方法与异络MO-2小型卫星阵列连接，并要求MEI4和ANKRD31蛋白，但不是轴分量REC8或Hormad1。我们提出重复的DNA序列赋予独特的染色质和高阶结构，这对重组至关重要。染色体突触突触细长阵列结构的塌陷，特别是，通过延迟或预防突触，可以重新编程卵母细胞以表现出在蛋白质中表现出的精子细胞样细胞蛋白酶。因此，PAR的性尺寸行为部分是在分析结构成熟，DSB的形成和配对和突触之间的成熟之间的性别之间的动力学差异。我们的调查结果建立了机械范式，用于减数分裂期间性染色体的重组。

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  • 来源
    《Nature》 |2020年第7812期|426-431|共6页
  • 作者

    Acquaviva Laurent; Boekhout Michiel; Karasu Mehmet E.; Brick Kevin; Pratto Florencia; Li Tao; van Overbeek Megan; Kauppi Liisa; Camerini-Otero R. Daniel; Jasin Maria; Keeney Scott;

  • 作者单位

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Univ Utrecht Oncode Inst UMC Utrecht Utrecht Netherlands;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Mem Sloan Kettering Canc Ctr Louis V Gerstner Jr Grad Sch Biomed Sci 1275 York Ave New York NY 10021 USA|Swiss Fed Inst Technol Zurich Switzerland;

    NIDDK Genet & Biochem Branch NIH Bethesda MD 20892 USA;

    NIDDK Genet & Biochem Branch NIH Bethesda MD 20892 USA;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Mem Sloan Kettering Canc Ctr Howard Hughes Med Inst New York NY 10021 USA;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Inscripta Inc Pleasanton CA USA;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Univ Helsinki Fac Med Helsinki Finland;

    NIDDK Genet & Biochem Branch NIH Bethesda MD 20892 USA;

    Mem Sloan Kettering Canc Ctr Louis V Gerstner Jr Grad Sch Biomed Sci 1275 York Ave New York NY 10021 USA|Mem Sloan Kettering Canc Ctr Dev Biol Program 1275 York Ave New York NY 10021 USA;

    Mem Sloan Kettering Canc Ctr Mol Biol Program 1275 York Ave New York NY 10021 USA|Mem Sloan Kettering Canc Ctr Louis V Gerstner Jr Grad Sch Biomed Sci 1275 York Ave New York NY 10021 USA|Mem Sloan Kettering Canc Ctr Howard Hughes Med Inst New York NY 10021 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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