A conserved function for a Caenorhabditis elegans Com1/Sae2/CtIP protein homolog in meiotic recombination
A conserved function for a Caenorhabditis elegans Com1/Sae2/CtIP protein homolog in meiotic recombination
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DOI：
10.1038/sj.emboj.7601916
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Loidl, Josef
中科院分区：
文献类型：
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作者：
Penkner, Alexandra;Portik-Dobos, Zsuzsanna;Loidl, Josef
在有丝分裂和减数分裂中，基因组的稳定性依赖于忠实的DNA修复。在这里，我们报道了一种秀丽隐杆线虫蛋白，我们发现它与哺乳动物修复相关蛋白CtIP和出芽酵母Com1/Sae2重组蛋白同源。com-1突变体显示正常的减数分裂染色体配对，但形成不规则的染色质聚集体，而不是分裂二价体。当减数分裂DNA双链断裂（dsb）形成时，它们似乎持续存在或经历不适当的修复。尽管存在dsb，但已知与dsb侧翼单链DNA （ssDNA）相关的重组蛋白RAD-51在com-1突变体中并未定位于减数分裂染色体。然而，突变体暴露于γ辐射会诱导RAD-51聚焦，这表明RAD-51加载失败是减数分裂（spo -11产生）dsb所特有的。这些结果表明，秀丽隐杆线虫COM-1在ssDNA尾部的产生中发挥了作用，ssDNA尾部可以装载RAD-51，侵入同源DNA束，从而启动重组。从蠕虫的同源性推断，我们期望哺乳动物肿瘤抑制因子CtIP的突变具有相似的表型。
Genome stability relies on faithful DNA repair both in mitosis and in meiosis. Here, we report on a Caenorhabditis elegans protein that we found to be homologous to the mammalian repair-related protein CtIP and to the budding yeast Com1/Sae2 recombination protein. A com-1 mutant displays normal meiotic chromosome pairing but forms irregular chromatin aggregates instead of diakinesis bivalents. While meiotic DNA double-strand breaks (DSBs) are formed, they appear to persist or undergo improper repair. Despite the presence of DSBs, the recombination protein RAD-51, which is known to associate with single-stranded DNA (ssDNA) flanking DSBs, does not localize to meiotic chromosomes in the com-1 mutant. Exposure of the mutant to gamma-radiation, however, induces RAD-51 foci, which suggests that the failure of RAD-51 to load is specific to meiotic (SPO-11-generated) DSBs. These results suggest that C. elegans COM-1 plays a role in the generation of ssDNA tails that can load RAD-51, invade homologous DNA tracts and thereby initiate recombination. Extrapolating from the worm homolog, we expect similar phenotypes for mutations in the mammalian tumor suppressor CtIP.