Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis.
Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis.
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DOI：
10.1371/journal.pgen.1002351
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发表时间：
2011-11
期刊：
影响因子：
4.5
通讯作者：
Burgess SM
中科院分区：
文献类型：
--
作者：
Ho HC;Burgess SM
在减数分裂过程中染色体的正确分离需要双链断裂（DSB）的形成和修复以形成交换。修复倾向于使用同源体而不是姐妹染色单体作为底物。Pch2是AAA +-ATP酶蛋白家族的保守成员，并且涉及广泛的减数分裂特异性过程，包括重组检查点、染色体轴的成熟、交换控制和突触。我们证明了Pch2在促进和调节同源物间的偏见和减数分裂重组检查点响应未加工的DSB通过激活轴蛋白Hop1和Mek1在芽殖酵母中的作用。我们表明，Pch2物理相互作用与假定的BRCT重复序列的N-末端区域的Xrs2，MRX复合物的一员，在未加工的DSB的网站上的行为。Pch 2、Xrs2和ATM直系同源物Tel 1在导致Hop1磷酸化的相同途径中起作用，独立于Rad17和ATR直系同源物Mec 1，其响应于单链DNA的存在。Xrs2的N-末端缺失概括了pch2 Δ表型，用于信号传导未切除的断裂。我们建议，与Xrs2的相互作用可能使Pch2重塑染色体结构附近的DSB的网站，从而促进访问Hop1的Tel 1激酶。此外，与Pch 2一样，Xrs 2也是染色体突触失败引起的检查点介导的延迟所必需的。有性生殖生物利用减数分裂产生配子（例如卵子和精子）。在减数分裂过程中，染色体数目减少到一半（单倍体），受精使它们的数目恢复到二倍体状态，从而使倍性可以在整个世代中保持。减数分裂包括两次连续的分裂（减数分裂I和减数分裂II），这两次分裂遵循一轮DNA复制。在减数分裂I中同源染色体分离，而在减数分裂II中姐妹染色单体分离。不能正确分离染色体导致非整倍体配子的形成，这是人类出生缺陷和妊娠丢失的主要原因。在大多数生物中，减数分裂I中的染色体分离需要减数分裂重组，其中故意引入的双链断裂（DSB）的修复在同源染色体之间产生物理连接。重要的是，DSB必须及时修复，并通过重组检查点与减数分裂周期协调。在这里，我们研究了Pch 2，AAA +-ATP酶蛋白，在减数分裂前期调节染色体事件的作用。我们发现Pch2与Tel 1（ATM的同源物）和MRX组分Xrs2一起功能，以发出钝端的、未加工的减数分裂重组DSB中间体的信号。此外，Pch 2和Xrs2之间的物理相互作用似乎在减数分裂过程中发挥额外的作用，独立于Tel 1功能。
Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA+-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes. Sexually reproductive organisms utilize meiosis to produce gametes (e.g. egg and sperm). During meiosis, chromosome numbers reduce to half (haploid) and fertilization restores their numbers to a diploid state so that ploidy can be maintained throughout generations. Meiosis involves two successive divisions (meiosis I and meiosis II) that follow a single round of DNA replication. In meiosis I homologous chromosomes segregate, whereas in meiosis II sister chromatids segregate. Failure to properly segregate chromosomes leads to the formation of aneuploid gametes, which are a leading cause of birth defects and pregnancy loss in humans. In most organisms, proper chromosome segregation in meiosis I requires meiotic recombination, where the repair of deliberately introduced double-strand breaks (DSBs) generates physical connections between homologous chromosomes. Importantly, DSBs must be repaired in a timely fashion and coordinated with the meiotic cycle by the recombination checkpoint. Here we investigated the role of Pch2, an AAA+-ATPase protein, in regulating chromosome events during meiotic prophase. We found Pch2 functions with Tel1 (homolog of ATM) and the MRX component Xrs2 to signal blunt-ended, unprocessed DSB intermediates of meiotic recombination. In addition, physical interaction between Pch2 and Xrs2 appears to play additional roles during meiosis, independent of Tel1 function.
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影响因子：
64.8
作者：
通讯作者：
--
完成减数分裂重组而不是突触需要小鼠Pachytene检查点2（TRIP13）。
影响因子：
4.5
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64.5
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Kleckner, N
影响因子：
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Hunter, Neil
影响因子：
5.8
作者：
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