Link Jana, Leubner Monika, Schmitt Johannes, Göb Eva, Benavente Ricardo, Jeang Kuan-Teh, Xu Rener, Alsheimer Manfred
Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Genet. 2014 Feb 27;10(2):e1004099. doi: 10.1371/journal.pgen.1004099. eCollection 2014 Feb.
LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE) attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun1(-/-) meiocytes attached telomeres retained the capacity to form bouquet-like clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun1(-/-) mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.
LINC复合体是进化上保守的核膜桥，由SUN（Sad-1/UNC-84）和KASH（Klarsicht/ANC-1/Syne/同源性）结构域蛋白组成。它们对于细胞核定位和核形态确定至关重要，还介导减数分裂端粒的核膜（NE）附着，这对于驱动同源染色体联会和重组至关重要。在小鼠中，SUN1和SUN2是减数分裂期间仅有的表达的SUN结构域蛋白，它们与减数分裂特异性的KASH5共定位。最近的研究表明，SUN1的缺失严重干扰减数分裂过程。SUN1的缺失会引发端粒附着缺陷并导致不育。在此，我们报道在SUN1缺陷的小鼠中减数分裂端粒附着并未完全丧失，而是许多端粒仍通过SUN2/KASH5-LINC复合体附着于核膜。在Sun1（-/-）减数分裂细胞中，附着的端粒保留了形成花束状簇的能力。此外，我们在Sun1（-/-）小鼠中检测到大量减数分裂后期重组事件。总之，这表明即使在没有SUN1的情况下，端粒附着及其在核膜内的移动本身仍可发挥功能。
