HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C-elegans

HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C-elegans
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DOI:
10.1101/gad.1348205
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发表时间:
2005-11-15
影响因子:
10.5
通讯作者:
Zetka, M
Zetka, M
中科院分区:
生物学1区
文献类型:
--
作者:
Couteau, F;Zetka, M

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在减数分裂过程中,负责同源配对、突触和重组的机制被精确协调,最终形成能够指导准确染色体分离的交叉。一个悬而未决的问题是,细胞如何确保减数分裂的结构标志--联会复合体(SC)--仅在对齐的同源染色体之间形成。在本研究中,我们发现秀丽隐杆线虫HIM-3基因家族中两个密切相关的成员具有突触调节功能。HTP-1通过阻止SC成分与未对齐和不成熟的染色体轴的关联,在功能上将同源排列与其通过突触稳定结合在一起;在没有蛋白质的情况下,染色体之间的非同源接触被不适当地稳定,导致广泛的非同源突触和交叉形成的急剧下降。在缺乏HTP-1和HTP-2的情况下,突触本身被取消,并且在htp-1突变体中观察到的SC成分与染色体的早期关联没有发生,这表明这些蛋白质在许可SC组装方面具有功能。此外,我们的结果表明,早期重组步骤发生在早期早期阶段的一个狭窄的机会窗口中,最终以SC组装结束,导致两个过程的机械耦合,以促进交叉。
During meiosis, the mechanisms responsible for homolog alignment, synapsis, and recombination are precisely coordinated to culminate in the formation of crossovers capable of directing accurate chromosome segregation. An outstanding question is how the cell ensures that the structural hallmark of meiosis, the synaptonemal complex (SC), forms only between aligned pairs of homologous chromosomes. In the present study, we find that two closely related members of the him-3 gene family in Caenorhabditis elegans function as regulators of synapsis. HTP-1 functionally couples homolog alignment to its stabilization by synapsis by preventing the association of SC components with unaligned and immature chromosome axes; in the absence of the protein, nonhomologous contacts between chromosomes are inappropriately stabilized, resulting in extensive nonhomologous synapsis and a drastic decline in chiasma formation. In the absence of both HTP-1 and HTP-2, synapsis is abrogated per se and the early association of SC components with chromosomes observed in htp-1 mutants does not occur, suggesting a function for the proteins in licensing SC assembly. Furthermore, our results suggest that early steps of recombination occur in a narrow window of opportunity in early prophase that ends with SC assembly, resulting in a mechanistic coupling of the two processes to promote crossing over.