By UNIVERSITY OF TOKYO
圖1. 上圖顯示非Rabl的組態。洋紅色的著絲粒分散在綠色的細胞核中。下圖顯示Rabl的組態。著絲粒在細胞核中，分佈不均。 (圖援用自原文)
Since the 1800s, scientists have noted the configuration of centromeres, a special chromosomal region that is vital for cell division, in the cell nucleus. However, up until now, the determining mechanisms and the biological significance of centromere distribution were poorly understood.
打從1800年代以來，科學家們已經注意到，細胞核中的著絲粒組態，這是一種對細胞分裂至關重要的特殊染色體區域。然而，到目前為止，有關著絲粒分佈的決定機制及生物學意義，未充分被瞭解。
Recently, researchers proposed a two-step regulatory mechanism that shapes centromere distribution. Their findings also indicate that centromere configuration in the nucleus plays a role in maintaining genome integrity.
最近，研究人員們提出了一種，塑造著絲粒分佈的兩步驟調節機制。他們的研究結果也顯示，細胞核中的著絲粒組態，在維持基因體完整性上，扮演一種角色。
The results were published today (August 1, 2022) in the journal Nature Plants. The study was led by researchers from the University of Tokyo and their collaborators.
此些結果，今天(2022年8月1日)發表於《自然•植物》期刊。該項研究，由來自日本東京大學的研究人員及其合作者們所領導。
Special chromosomal domains known as centromeres are pulled to the opposite ends of the cell during the process of cell division. After cell division is complete and the cell nucleus is constructed, centromeres are spatially distributed in the nucleus.
在細胞分裂過程中，被通稱為著絲粒的特殊染色體結構域，被拉到細胞的另一端。在細胞分裂完成及形成細胞核後，空間上著絲粒被分佈於細胞核中。
If the distribution of centromeres pulled to the two poles remains unchanged, the cell nucleus will have centromeres grouped at just one side of the nucleus. This uneven distribution of centromeres is called Rabl configuration, after Carl Rabl, the 19th-century cytologist. Some species’ nuclei show a dispersed distribution of centromeres instead. This is known as non-Rabl configuration.
倘若被拉向兩端之著絲粒的分佈保持不變，則細胞核會有著絲粒，僅集中在此細胞核的一側。這種著絲粒的不均勻分佈，以19 世紀細胞學家，Carl Rabl的名子命名，被稱為Rabl組態。有些物種的細胞核，反而呈現分散的著絲粒分佈。這被通稱為非Rabl組態。
“The biological function and molecular mechanism of the Rabl or non-Rabl configuration has been a mystery across the centuries,” said corresponding author Sachihiro Matsunaga, professor at the University of Tokyo’s Graduate School of Frontier Sciences. “We successfully revealed the molecular mechanism to construct the non-Rabl configuration.”
通訊撰文人，東京大學前沿科學研究生院教授，Sachihiro Matsunaga宣稱：「Rabl或非Rabl組態的生物學功能及分子機制，一直是一項跨世紀之謎。我們成功揭露了，構成非Rabl組態的分子機制。」
圖2. 於細胞核(綠色)中，著絲粒(洋紅色)的不均勻分佈。 (圖援用自原文)
The scientists studied the plant Arabidopsis thaliana, known also as thale cress and a specimen that is known to have non-Rabl configuration, and its mutant form that had a Rabl configuration.
此些科學家研究了，也被稱為擬南芥的阿拉伯芥這種植物。這是一種已知具有非Rabl組態，及其具有Rabl組態之突變形式的標本。
Through their work, they found that protein complexes known as condensin II (CII) and protein complexes known as the linker of nucleoskeleton and cytoskeleton (LINC) complex work together to determine centromere distribution during cell division.
經由他們的研究，他們發現被通稱為凝聚素II(CII)的蛋白複合物，與被通稱為核骨架及細胞骨架(LINC)之連接物的蛋白質複合物一起運作，來決定細胞分裂期間的著絲粒分佈。
“The centromere distribution for non-Rabl configuration is regulated independently by the CII– LINC complex and a nuclear lamina protein known as CROWDED NUCLEI (CRWN),” Matsunaga said.
Matsunaga宣稱：「非Rabl組態的著絲粒分佈，由CII與LINC複合物及一種被稱為擁擠核(CROWDED NUCLEI (CRWN))的核層蛋白所獨立調節。」
The first step of the two-step regulatory mechanism of centromere distribution that the researchers uncovered was that the CII-LINC complex mediates the scattering of centromeres from late anaphase to telophase — two phases at the end of cell division. The second step of the process is that the CRWNs stabilize the scattered centromeres on nuclear lamina within the nucleus.
此些研究人員揭露著絲粒分佈之兩步驟調節機制的第一步是，CII-LINC複合物居間調節，著絲粒從後期之後期到末期(細胞分裂結束時的兩個階段)的分散。該過程的第二步驟是，CRWN穩定於核內之核層上分散的著絲粒。
Next, to explore the biological significance, the researchers analyzed the gene expression in A. thaliana and in its Rabl-structure mutant. Because a change in the spatial arrangement of centromeres also changes the spatial arrangement of genes, the researchers expected to find differences in gene expression, but this hypothesis proved to be incorrect.
接下來，為了探索生物學的意義，此些研究人員分析了，於擬南芥及其Rabl 組態突變體中的基因表現。因為，於著絲粒之空間排列上的改變，也會改變基因的空間排列。因而，此些研究人員希望能發現，於基因表現上的差異。不過，此假設經證實不正確。
However, when DNA damage stress was applied, the mutant grew organs at a slower rate than the normal plant.
然而，當被施加DNA損傷壓力時，這種突變體以比正常植物慢的速度使器官成長。
“This suggests that precise control of centromere spatial arrangement is required for organ growth in response to DNA damage stress, and there is no difference in tolerance to DNA damage stress between organisms with the non-Rabl and Rabl,” Matsunaga said. “This suggests that the appropriate spatial arrangement of DNA in the nucleus regardless of Rabl configuration is important for stress response.”
Matsunaga宣稱：「這暗示，在對DNA損傷壓力作出反應上，器官生長需要精確控制著絲粒空間的排列。因此，在對DNA損傷壓力的耐受性上，於具有非Rabl與Rabl的生物之間沒有差異。這暗示，無論Rabl組態為何，於細胞核中，DNA的適當空間排列，對於壓力反應皆重要。」
According to Matsunaga, the next steps are to identify the power source that changes the spatial arrangement of specific DNA regions and the mechanism that recognizes specific DNA.
根據Matsunaga的說法，接下來的步驟是，確認改變特定DNA區域之空間排列的動力源，及識別特定DNA的機制。
“Such findings will lead to the development of technology for artificially arranging DNA in the cell nucleus in an appropriate spatial arrangement,” he said. “It is expected that this technology will make it possible to create stress-resistant organisms, as well as to impart new properties and functions by altering the spatial arrangement of DNA rather than editing its nucleotide sequence.”
他宣稱：「此些這類研究發現將導致，在細胞核中，以人為之適當空間排列方式，來排列DNA的技術開發。除了藉由改變DNA的空間排列，而不是編輯其核苷酸序列，來賦予新的特性及功能之外，也被預期此技術，將使其可能創造出抗壓力的生物。」
網址：https://scitechdaily.com/scientists-solve-a-mystery-across-the-centuries/
翻譯：許東榮
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