Liebe B, Petukhova G, Barchi M, Bellani M, Braselmann H, Nakano T, Pandita T K, Jasin M, Fornace A, Meistrich M L, Baarends W M, Schimenti J, de Lange T, Keeney S, Camerini-Otero R D, Scherthan H
Max-Planck-Inst. for Molecular Genetics, Ihnestr. 73, D-14195 Berlin, Germany.
Exp Cell Res. 2006 Nov 15;312(19):3768-81. doi: 10.1016/j.yexcr.2006.07.019. Epub 2006 Aug 2.
Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-), Terf1(+/-) and Hr6b(-/-) spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.
减数分裂使同源染色体配对并分离，从而形成单倍体生殖细胞，以补偿受精时基因组的加倍。许多真核生物物种中的同源染色体配对依赖于减数分裂前期I早期DNA双链断裂（DSB）的形成，此时端粒开始在核周边聚集（花束期）。通过荧光原位杂交标准，我们观察到，在缺乏重组、泛素缀合和端粒长度控制所需蛋白质的雄性小鼠中，前细线期中期和花束期的频率发生了改变。缺乏重组蛋白SPO11、MEI1、MLH1、KU80、泛素缀合酶HR6B的雄性小鼠，以及只有一个端粒长度调节因子Terf1拷贝的小鼠，前细线期中期精母细胞的通常较低频率显著增加。在Atm(-/-)、Spo11(-/-)、Mei1(m1Jcs/m1Jcs)、Mlh1(-/-)、Terf1(+/-)和Hr6b(-/-)精子发生过程中，花束期显著富集，但在缺乏重组蛋白DMC1和HOP2、非同源末端连接DNA修复因子KU80以及ATM下游效应因子GADD45a的小鼠中则不然。精子形成有缺陷的小鼠（Tnp1(-/-)、Gmcl1(-/-)、Asm(-/-)）表现出野生型的前细线期中期和花束期频率。Spo11(-/-)Atm(-/-)精子发生过程中花束期精母细胞的频率较低，这表明DSB导致了与Atm(-/-)相关的花束期退出缺陷。DSB修复早期有缺陷的小鼠（Dmc1(-/-)、Hop2(-/-)）中花束期频率的变化不显著，这表明ATM对花束期持续时间有特异性影响。总之，似乎有几种途径影响哺乳动物减数分裂中端粒的动态变化。
