The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse.
The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse.
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DOI：
10.1371/journal.pgen.1003261
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Alsheimer M
中科院分区：
文献类型：
--
作者：
Link J;Jahn D;Schmitt J;Göb E;Baar J;Ortega S;Benavente R;Alsheimer M
核层是核膜的结构支架，在核组织和维持核的稳定性和形状中起着中心作用。过去，许多严重的人类疾病已被确定与层粘连蛋白突变有关。对这一课题的广泛研究为了解核层的功能提供了新的重要线索。这些研究表明，椎板是一个复杂的多功能平台，结合了结构和调节功能。在这里，我们报道，除了先前证明的对体细胞分化和维持的意义外，核层也是生殖细胞发育的重要决定因素。缺乏短减数分裂特异性a型纤层蛋白C2的雄性和雌性小鼠都有严重的减数分裂缺陷，至少在雄性小鼠中会导致不育。详细分析表明，纤层蛋白C2是端粒驱动的减数分裂染色体动态重定位所必需的。层粘连蛋白C2的缺失影响同源物的精确突触并干扰减数分裂双链断裂修复。综上所述，我们的数据解释了核层如何在机械水平上对减数分裂染色体行为和精确的基因组单倍体化做出贡献。二倍体生殖系细胞必须经过减数分裂才能产生单倍体配子。单倍体化包括同源染色体的配对和重组，这是它们正确分离的先决条件。同源染色体的配对需要它们在减数分裂核内的主动重新定位，这取决于端粒与核膜的相互作用。这种动态的联系对于忠实的减数分裂是至关重要的，因此对生育至关重要。然而，人们对端粒和核膜组分之间的关系知之甚少。在这里，我们研究了核层的作用，核层是一种与核膜密切相关的结构支架。在体细胞中，层是染色质组织的关键参与者，具有核结构维持和转录调节等多种功能。为了了解其在减数分裂中的作用，我们研究了哺乳动物减数分裂细胞中唯一表达的a型层粘连蛋白C2。我们证明了层粘连蛋白C2对于减数分裂端粒的及时重新定位是必不可少的。在缺乏它的情况下，同源染色体的突触和双链断裂修复受到严重影响。这些多重减数分裂缺陷导致男性不育。我们得出结论，核层通过促进减数分裂染色体的运动直接有助于生育。
The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this topic has provided novel important clues about nuclear lamina function. These studies have contributed to the knowledge that the lamina constitutes a complex multifunctional platform combining both structural and regulatory functions. Here, we report that, in addition to the previously demonstrated significance for somatic cell differentiation and maintenance, the nuclear lamina is also an essential determinant for germ cell development. Both male and female mice lacking the short meiosis-specific A-type lamin C2 have a severely defective meiosis, which at least in the male results in infertility. Detailed analysis revealed that lamin C2 is required for telomere-driven dynamic repositioning of meiotic chromosomes. Loss of lamin C2 affects precise synapsis of the homologs and interferes with meiotic double-strand break repair. Taken together, our data explain how the nuclear lamina contributes to meiotic chromosome behaviour and accurate genome haploidization on a mechanistic level. Diploid germ line cells have to undergo meiosis to produce haploid gametes. Haploidization involves pairing and recombination of homologous chromosomes as a prerequisite for their proper segregation. Pairing of homologous chromosomes requires their active repositioning within meiotic nuclei, which depends on the interaction of telomeres with the nuclear envelope. This dynamic association is vital for a faithful meiosis and thus crucial for fertility. However, very little is known about the relationship between telomeres and nuclear envelope components. Here, we have investigated the role of the nuclear lamina, a structural scaffold that is intimately associated with the inner nuclear membrane. In somatic cells, the lamina is a key player in chromatin organization and fulfils various functions such as nuclear structure maintenance and regulation of transcription. In order to understand its role in meiosis, we investigated lamin C2, the only A-type lamin isoform expressed in mammalian meiotic cells. We demonstrate that lamin C2 is essential for timely repositioning of meiotic telomeres. In its absence, synapsis of homologous chromosomes and double-strand break repair are severely affected. These multiple meiotic defects lead to infertility in males. We conclude that the nuclear lamina contributes directly to fertility through facilitating meiotic chromosome movements.
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影响因子：
64.5
作者：
Chikashige, Y;Tsutsumi, C;Hiraoka, Y
通讯作者：
Hiraoka, Y
影响因子：
64.5
作者：
Conrad, Michael N.;Lee, Chih-Ying;Dresser, Michael E.
通讯作者：
Dresser, Michael E.
影响因子：
3.7
作者：
Alsheimer, M;Benavente, R
通讯作者：
Benavente, R
DOI：
10.1007/978-3-642-14773-9_12
发表时间：
2011-01-01
期刊：
EPIGENETICS AND HUMAN REPRODUCTION
影响因子：
--
作者：
Alsheimer, Manfred;Jahn, Daniel;Benavente, Ricardo
通讯作者：
Benavente, Ricardo
DOI：
10.1007/978-1-60761-103-5_21
发表时间：
2009-01-01
期刊：
MEIOSIS, VOL 2: CYTOLOGICAL METHODS
影响因子：
--
作者：
de Boer, Esther;Lhuissier, Franck G. P.;Heyting, Christa
通讯作者：
Heyting, Christa