减数分裂是有性生殖生物配子产生的必需过程.在细胞进入减数分裂前,其染色体复制1次,但启动分裂后,细胞进行二次分裂,从而产生染色体数目减半的配子.减数分裂Ⅰ前期同源染色体的配对、联会、重组以及减数分裂Ⅰ后期同源染色体的分离是...减数分裂是有性生殖生物配子产生的必需过程.在细胞进入减数分裂前,其染色体复制1次,但启动分裂后,细胞进行二次分裂,从而产生染色体数目减半的配子.减数分裂Ⅰ前期同源染色体的配对、联会、重组以及减数分裂Ⅰ后期同源染色体的分离是减数分裂的基本特征,而这些减数分裂特异事件的按时、依序发生则有赖于减数分裂Ⅰ前期程序性D N A双链断裂(D S B)的产生和以同源染色体为模板进行的同源重组修复.本文将对减数分裂特别是减数分裂Ⅰ前期染色体的行为进行简要综述,并就其分子基础和机制进行分析讨论.展开更多
Meiosis is pivotal for sexual reproduction and fertility. Meiotic programmed DNA double-strand breaks(DSBs) initiate homologous recombination, ensuring faithful chromosome segregation and generation of gametes. Howeve...Meiosis is pivotal for sexual reproduction and fertility. Meiotic programmed DNA double-strand breaks(DSBs) initiate homologous recombination, ensuring faithful chromosome segregation and generation of gametes. However, few studies have focused on meiotic DSB formation in human reproduction.Here, we report four infertile siblings born to a consanguineous marriage, with three brothers suffering from non-obstructive azoospermia and one sister suffering from unexplained infertility with normal menstrual cycles and normal ovary sizes with follicular activity. An autosomal recessive mutation in TOP6BL was found co-segregating with infertility in this family. Investigation of one male patient revealed failure in programmed meiotic DSB formation and meiotic arrest prior to pachytene stage of prophase I.Mouse models carrying similar mutations to that in patients recapitulated the spermatogenic abnormalities of the patient. Pathogenicity of the mutation in the female patient was supported by observations in mice that meiotic programmed DSBs failed to form in mutant oocytes and oocyte maturation failure due to absence of meiotic recombination. Our study thus illustrates the phenotypical characteristics and the genotype-phenotype correlations of meiotic DSB formation failure in humans.展开更多
文摘减数分裂是有性生殖生物配子产生的必需过程.在细胞进入减数分裂前,其染色体复制1次,但启动分裂后,细胞进行二次分裂,从而产生染色体数目减半的配子.减数分裂Ⅰ前期同源染色体的配对、联会、重组以及减数分裂Ⅰ后期同源染色体的分离是减数分裂的基本特征,而这些减数分裂特异事件的按时、依序发生则有赖于减数分裂Ⅰ前期程序性D N A双链断裂(D S B)的产生和以同源染色体为模板进行的同源重组修复.本文将对减数分裂特别是减数分裂Ⅰ前期染色体的行为进行简要综述,并就其分子基础和机制进行分析讨论.
基金supported by the National Key Research and Developmental Program of China (2018YFC1003700, 2016YFC1000600, 2018YFC1003400 and 2018YFC1004700)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000)the National Natural Science Foundation of China (31890780, 31630050, 31871514 and 31771668)。
文摘Meiosis is pivotal for sexual reproduction and fertility. Meiotic programmed DNA double-strand breaks(DSBs) initiate homologous recombination, ensuring faithful chromosome segregation and generation of gametes. However, few studies have focused on meiotic DSB formation in human reproduction.Here, we report four infertile siblings born to a consanguineous marriage, with three brothers suffering from non-obstructive azoospermia and one sister suffering from unexplained infertility with normal menstrual cycles and normal ovary sizes with follicular activity. An autosomal recessive mutation in TOP6BL was found co-segregating with infertility in this family. Investigation of one male patient revealed failure in programmed meiotic DSB formation and meiotic arrest prior to pachytene stage of prophase I.Mouse models carrying similar mutations to that in patients recapitulated the spermatogenic abnormalities of the patient. Pathogenicity of the mutation in the female patient was supported by observations in mice that meiotic programmed DSBs failed to form in mutant oocytes and oocyte maturation failure due to absence of meiotic recombination. Our study thus illustrates the phenotypical characteristics and the genotype-phenotype correlations of meiotic DSB formation failure in humans.
