The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination.
The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination.
复制标题
单链 DNA 结合蛋白 MEIOB 作为减数分裂重组的剂量敏感调节剂
DOI：
10.1093/nar/gkaa1016
复制
发表时间：
2020-12-02
影响因子：
14.9
通讯作者：
Wang PJ
中科院分区：
文献类型：
--
作者：
Guo R;Xu Y;Leu NA;Zhang L;Fuchs SY;Ye L;Wang PJ
减数分裂重组使亲本染色体之间的遗传信息相互交换成为可能，对生育力至关重要。MEIOB是一种减数分裂特异性ssDNA结合蛋白，调节早期减数分裂重组。在这里，我们报告，人类不育相关的错义突变（N64 I）MEIOB导致蛋白质降解和减少小鼠睾丸中的交叉形成。虽然MEIOB N64I取代与人类不育相关，但点突变小鼠尽管有减数分裂缺陷，但仍能生育。Meiob诱变鉴定丝氨酸67为MEIOB的关键残基。在生物化学上，这两个突变（N64 I和S67缺失）导致MEIOB的自聚集和蛋白质半衰期的急剧降低。这两个点突变体的分子遗传学分析揭示了一个重要的作用，MEIOB在交叉形成后期减数分裂重组。此外，我们发现MEIOB蛋白水平与减数分裂缺陷的严重程度直接相关。我们的结果表明，MEIOB以剂量依赖性方式调节减数分裂重组。
Meiotic recombination enables reciprocal exchange of genetic information between parental chromosomes and is essential for fertility. MEIOB, a meiosis-specific ssDNA-binding protein, regulates early meiotic recombination. Here we report that the human infertility-associated missense mutation (N64I) in MEIOB causes protein degradation and reduced crossover formation in mouse testes. Although the MEIOB N64I substitution is associated with human infertility, the point mutant mice are fertile despite meiotic defects. Meiob mutagenesis identifies serine 67 as a critical residue for MEIOB. Biochemically, these two mutations (N64I and S67 deletion) cause self-aggregation of MEIOB and sharply reduced protein half-life. Molecular genetic analyses of both point mutants reveal an important role for MEIOB in crossover formation in late meiotic recombination. Furthermore, we find that the MEIOB protein levels directly correlate with the severity of meiotic defects. Our results demonstrate that MEIOB regulates meiotic recombination in a dosage-dependent manner.
登录
查看更多内容
影响因子：
4.5
作者：
Holloway JK;Booth J;Edelmann W;McGowan CH;Cohen PE
通讯作者：
Cohen PE
影响因子：
4.6
作者：
Ishishita S;Matsuda Y;Kitada K
通讯作者：
Kitada K
影响因子：
8.8
作者：
Brandsma, Inger;Sato, Koichi;Zelensky, Alex N.
通讯作者：
Zelensky, Alex N.
影响因子：
4.4
作者：
Nakayama, K;Furusu, A;Kitamura, M
通讯作者：
Kitamura, M
影响因子：
64.8
作者：
Dixon, Jesse R.;Selvaraj, Siddarth;Yue, Feng;Kim, Audrey;Li, Yan;Shen, Yin;Hu, Ming;Liu, Jun S.;Ren, Bing
通讯作者：
Ren, Bing