The Drosophila zinc finger protein trade embargo is required for double strand break formation in meiosis.

The Drosophila zinc finger protein trade embargo is required for double strand break formation in meiosis.
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DOI:
10.1371/journal.pgen.1002005
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发表时间:
2011-02
期刊:
影响因子:
4.5
通讯作者:
Hawley RS
Hawley RS
中科院分区:
生物学2区
文献类型:
--
作者:
Lake CM;Nielsen RJ;Hawley RS

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减数分裂中的同源重组是由双链断裂(DSB)的程序性诱导启动的。虽然果蝇Spo11同源基因Mei-W68在减数分裂前期诱导DSB是必需的,但只有一种蛋白质(Mei-P22)被证明发挥这一功能。我们在这里表明,染色质相关蛋白贸易禁运(TREM)是一种C2H2锌指蛋白,需要将Mei-P22定位到减数分裂染色体上的离散焦点,从而促进DSB的形成,使TREM成为果蝇卵母细胞DSB形成过程中已知的最早功能。我们推测,TREM可能通过引导Mei-P22与DSB形成的首选位置结合,或者通过改变染色质结构以允许Mei-P22形成焦点来发挥作用。有性繁殖生物产生可存活后代的能力取决于它们忠实地执行减数分裂的能力。减数分裂是一组特殊的两个细胞分裂,确保每个精子和卵子只收到每对染色体的一个副本。因此,在人类女性中,尽管几乎所有的体细胞都带有23对同源染色体(总共46条染色体),但卵子只需要拥有每条染色体的一个副本(总共23条)。染色体数目的减少需要三个基本步骤:同源染色体配对,通过重组将这些对连接起来,以及在第一次减数分裂时将这些对分离成两个子细胞。不幸的是,人们对选择重组位点的机制(S)知之甚少。在这里,我们描述了一种名为TREM的果蝇蛋白质,它既与减数分裂染色体结合,又定义了果蝇重组启动的第一个已知步骤。我们对TREM蛋白的功能解剖和突变缺陷的性质的研究为重组是如何启动的谜团提供了重要线索。这些线索将帮助我们理解细胞如何控制这一关键的减数分裂过程。
Homologous recombination in meiosis is initiated by the programmed induction of double strand breaks (DSBs). Although the Drosophila Spo11 ortholog Mei-W68 is required for the induction of DSBs during meiotic prophase, only one other protein (Mei-P22) has been shown to be required for Mei-W68 to exert this function. We show here that the chromatin-associated protein Trade Embargo (Trem), a C2H2 zinc finger protein, is required to localize Mei-P22 to discrete foci on meiotic chromosomes, and thus to promote the formation of DSBs, making Trem the earliest known function in the process of DSB formation in Drosophila oocytes. We speculate that Trem may act by either directing the binding of Mei-P22 to preferred sites of DSB formation or by altering chromatin structure in a manner that allows Mei-P22 to form foci. The ability of sexually reproducing organisms to produce viable offspring depends on their ability to faithfully execute meiosis. Meiosis is a specialized set of two cell divisions that ensures that each sperm and egg receives only one copy of each pair of chromosomes. Thus, in human females, although virtually all somatic cells carry 23 pairs of homologous chromosomes (for a total of 46 chromosomes), the egg needs to possess only one copy of each chromosome (for a total of 23). This reduction in chromosome number requires three basic steps: the pairing of homologous chromosomes, the linking of those pairs by recombination, and the separation of those pairs into two daughter cells at the first meiotic division. Unfortunately, little is known about the mechanism(s) by which the sites of recombination are chosen. Here we describe a Drosophila protein called Trem that both binds to meiotic chromosomes and defines the first known step of recombination initiation in Drosophila. Our studies of the functional anatomy of the Trem protein and the nature of the mutant defect provide important clues to the puzzle of how recombination is initiated. Such clues will help us understand how the cell controls this critical meiotic process.
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