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DNA“双链断裂”的控制

摘要 : 美国纪念斯隆-凯特琳癌症中心和康奈尔大学的研究人员在酵母研究中,发现了两个在遗传上截然不同的的DSB控制路径。相关文章发表于2014年4月6日的《Nature》杂志上。

DNA“双链断裂”(DSBs)有造成损害的潜力,尽管有些时候(如在减数分裂和免疫球蛋白形成过程中)程序化的链断裂是正常细胞功能所必需的。

由 Scott Keeney 及同事完成的一项新的研究考察酵母减数分裂细胞中的这些程序化断裂的数量是怎样被控制的。他们发现了两个在遗传上截然不同的的DSB控制路径:一个与同源染色体的成功配对有关;另一个与减数分裂细胞周期的调控有关。后一个过程涉及ZMM蛋白,它们是在减数分裂交换(meiotic crossover)的控制中所涉及的一组蛋白,过去被认为只在DSB形成过程的下游发挥作用。

原文摘要:

Homologue engagement controls meiotic DNA break number and distribution

Drew Thacker, Neeman Mohibullah, Xuan Zhu & Scott Keeney

Meiotic recombination promotes genetic diversification as well as pairing and segregation of homologous chromosomes, but the double-strand breaks (DSBs) that initiate recombination are dangerous lesions that can cause mutation or meiotic failure. How cells control DSBs to balance between beneficial and deleterious outcomes is not well understood. Here we test the hypothesis that DSB control involves a network of intersecting negative regulatory circuits. Using multiple complementary methods, we show that DSBs form in greater numbers in Saccharomyces cerevisiaecells lacking ZMM proteins, a suite of recombination-promoting factors traditionally regarded as acting strictly downstream of DSB formation. ZMM-dependent DSB control is genetically distinct from a pathway tying break formation to meiotic progression through the Ndt80 transcription factor. These counterintuitive findings suggest that homologous chromosomes that have successfully engaged one another stop making breaks. Genome-wide DSB maps uncover distinct responses by different subchromosomal domains to the ZMM mutation zip3 (also known as cst9), and show that Zip3 is required for the previously unexplained tendency of DSB density to vary with chromosome size. Thus, feedback tied to ZMM function contributes in unexpected ways to spatial patterning of recombination.

对应Nature杂志: 2014年6月12日Nature杂志精选

来源: Nature中文 浏览次数:57

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