Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1
Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1
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DOI：
10.1091/mbc.e05-05-0465
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Hollingsworth, NM
中科院分区：
文献类型：
--
作者：
Niu, HY;Wan, L;Hollingsworth, NM
减数分裂重组与有丝分裂重组的不同之处在于 DSB 是使用同源染色体而不是姐妹染色单体进行修复的。伴侣选择的这种变化部分是由于减数分裂特异性激酶 Mek1 与其他两种减数分裂特异性蛋白 Hop1 和 Red1 形成复合物而产生的姐妹染色单体修复 (BSCR) 障碍。 HOP1 包含两个功能域，称为 N 和 C 域。对特异性失活 C 结构域 (hop1-K593A) 的点突变的分析表明，N 结构域足以将 Hop1 定位到染色体以及 Red1 和 Hop1 相互作用。 C 结构域是孢子活力、染色体突触和防止不依赖 DMC1 的 DSB 修复所必需的，这表明它在 BSCR 中发挥作用。所有 hop1-K593A 表型都可以通过异位二聚化结构域与 Mek1 的融合来绕过，这表明 C 结构域的功能是促进 Mek1 二聚化。 Hop1是一种DSB依赖性磷蛋白，其磷酸化需要C结构域的存在，但独立于MEK1。这些结果表明，Hop1 响应 DSB 的磷酸化通过 Hop1 C 结构域触发 Mek1 二聚化，从而使 Mek1 能够磷酸化目标蛋白，从而防止姐妹染色单体修复 DSB。
Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1. HOP1 contains two functional domains, called the N and C domains. Analysis of a point mutation that specifically inactivates the C domain (hop1-K593A) reveals that the N domain is sufficient for Hop1 localization to chromosomes and for Red1 and Hop1 interactions. The C domain is needed for spore viability, for chromosome synapsis, and for preventing DMC1-independent DSB repair, indicating it plays a role in the BSCR. All of the hop1-K593A phenotypes can be bypassed by fusion of ectopic dimerization domains to Mek1, suggesting that the function of the C domain is to promote Mek1 dimerization. Hop1 is a DSB-dependent phosphoprotein, whose phosphorylation requires the presence of the C domain, but is independent of MEK1. These results suggest a model in which Hop1 phosphorylation in response to DSBs triggers dimerization of Mek1 via the Hop1 C domain, thereby enabling Mek1 to phosphorylate target proteins that prevent repair of DSBs by sister chromatids.