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
Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double st...Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double strand break repair mechanisms were analyzed in Cyclin A1 （Ccnal）; p53- and Ccnal; Atm-double knockout mice. Results： The block in spermatogenesis observed in Cyclin A1-/- （Ccnal-/-） testes at the mid-diplotene stage is associated with polynucleated giant cells. We found that Ccnal-deficient testes and especially the giant cells accumulate unrepaired DNA double-strand breaks, as detected by immunohistochemistry for phosphorylated H2AX. In addition, the giant cells escape from apoptosis. The development of giant cells occurred in meiotic prophase I, because testes lacking ATM, which are known to develop spermatogenic arrest earlier than prophase I, do not develop giant cells in the absence of cyclin A1. Cyclin A1 interacted with p53 and phosphorylated p53 in complex with CDK2. Interestingly, p53-deficiency significantly increased the number of giant cells in Ccnal-deficient testes. Gene expression analyses of a panel of DNA repair genes in the mutant testes revealed that none of the genes examined were consistently misregulated in the absence of cyclin A1. Conclusion： Ccnal-deficiency in spermatogenesis is associated with defects in DNA double-strand break repair, which is enhanced by loss of p53.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.
文摘Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double strand break repair mechanisms were analyzed in Cyclin A1 （Ccnal）; p53- and Ccnal; Atm-double knockout mice. Results： The block in spermatogenesis observed in Cyclin A1-/- （Ccnal-/-） testes at the mid-diplotene stage is associated with polynucleated giant cells. We found that Ccnal-deficient testes and especially the giant cells accumulate unrepaired DNA double-strand breaks, as detected by immunohistochemistry for phosphorylated H2AX. In addition, the giant cells escape from apoptosis. The development of giant cells occurred in meiotic prophase I, because testes lacking ATM, which are known to develop spermatogenic arrest earlier than prophase I, do not develop giant cells in the absence of cyclin A1. Cyclin A1 interacted with p53 and phosphorylated p53 in complex with CDK2. Interestingly, p53-deficiency significantly increased the number of giant cells in Ccnal-deficient testes. Gene expression analyses of a panel of DNA repair genes in the mutant testes revealed that none of the genes examined were consistently misregulated in the absence of cyclin A1. Conclusion： Ccnal-deficiency in spermatogenesis is associated with defects in DNA double-strand break repair, which is enhanced by loss of p53.
