Found: A new form of DNA in our cellsScientists have tracked down an elusive 'tangled knot' of DNA
重大發現：我們細胞中的一種新形式的DNA
科學家已經追踪到一個難以捉摸的“糾結”DNA
DATE:April 23, 2018
Source: Garvan Institute of Medical Research
In a world first, researchers have identified a new DNA structure -- called the i-motif -- inside cells. A twisted 'knot' of DNA, the i-motif has never before been directly seen inside living cells.
In a world first, Australian researchers have identified a new DNA structure -- called the i-motif -- inside cells. A twisted 'knot' of DNA, the i-motif has never before been directly seen inside living cells.
The new findings, from the Garvan Institute of Medical Research, are published today in the leading journal Nature Chemistry.
Deep inside the cells in our body lies our DNA. The information in the DNA code -- all 6 billion A, C, G and T letters -- provides precise instructions for how our bodies are built, and how they work.
The iconic 'double helix' shape of DNA has captured the public imagination since 1953, when James Watson and Francis Crick famously uncovered the structure of DNA. However, it's now known that short stretches of DNA can exist in other shapes, in the laboratory at least -- and scientists suspect that these different shapes might play an important role in how and when the DNA code is 'read'.
首先，澳大利亞的研究人員在細胞內發現了一種新的DNA結構 - 稱為i-基元。 一個扭曲的“DNA結”，i-motif以前從未在活細胞內直接看到過。
來自Garvan醫學研究所的新發現今天發表在主要期刊Nature Chemistry上 。
我們體內的細胞深處是我們的DNA。 DNA代碼中的信息 - 全部60億A，C， G和T字母 - 為我們的身體如何構建以及如何工作提供了精確的說明。
自1953年以來，詹姆斯沃森和弗朗西斯克里克著名揭開DNA的結構，標誌性的“雙螺旋”DNA形狀已經吸引了公眾的想像力。 然而，現在已知DNA短片段可以以其他形式存在，至少在實驗室中 - 科學家們懷疑這些不同的形狀可能在DNA代碼被讀取的時間和方式上發揮重要作用。新形狀與雙鏈DNA雙螺旋完全不同。
“當我們大多數人想到DNA時，我們會想到雙螺旋結構，”Daniel Christ副教授（加文公司抗體治療實驗室負責人）說。 “這項新研究提醒我們，存在完全不同的DNA結構 - 對我們的細胞很重要。”
The new shape looks entirely different to the double-stranded DNA double helix.
"When most of us think of DNA, we think of the double helix," says Associate Professor Daniel Christ (Head, Antibody Therapeutics Lab, Garvan) who co-led the research. "This new research reminds us that totally different DNA structures exist -- and could well be important for our cells."
"The i-motif is a four-stranded 'knot' of DNA," says Associate Professor Marcel Dinger (Head, Kinghorn Centre for Clinical Genomics, Garvan),.who co-led the research with A/Prof Christ.
"In the knot structure, C letters on the same strand of DNA bind to each other -- so this is very different from a double helix, where 'letters' on opposite strands recognise each other, and where Cs bind to Gs [guanines]."
Although researchers have seen the i-motif before and have studied it in detail, it has only been witnessed in vitro -- that is, under artificial conditions in the laboratory, and not inside cells.
雖然研究人員之前已經看到了i-motif並對其進行了詳細的研究，但它僅在體外見證過 - 即在實驗室的人工條件下，而不是在細胞內。事實上，這個領域的科學家們已經在討論是否所有活物內部都會存在i-motif“節點” - 這個問題由新發現解決了。
為了檢測細胞內的i圖案，研究人員開發了一種精確的新工具 - 抗體分子的片段 - 能夠以高親和力特異性識別並附著於i-圖案。 到目前為止，缺乏針對i圖案的抗體嚴重阻礙了他們對其作用的理解。
關鍵的是，抗體片段沒有檢測到螺旋形式的DNA，也沒有識別'G-四聯體結構'（一種結構相似的四鏈DNA排列）。
利用這一新工具，研究人員在一系列人類細胞系中發現了'i-motifs'的位置。 使用熒光技術來查明i圖案的位置，他們在細胞核內鑑定出許多綠色的斑點，這表明了i圖案的位置。
Mahdi Zeraati博士說：“最令我們激動的是，我們可以看到綠色的斑點 - 我的母題 - 隨著時間的推移而出現和消失，所以我們知道它們正在形成，溶解並再次形成，”他的研究支撐著研究結果。
In fact, scientists in the field have debated whether i-motif 'knots' would exist at all inside living things -- a question that is resolved by the new findings.
To detect the i-motifs inside cells, the researchers developed a precise new tool -- a fragment of an antibody molecule -- that could specifically recognise and attach to i-motifs with a very high affinity. Until now, the lack of an antibody that is specific for i-motifs has severely hampered the understanding of their role.
Crucially, the antibody fragment didn't detect DNA in helical form, nor did it recognise 'G-quadruplex structures' (a structurally similar four-stranded DNA arrangement).
With the new tool, researchers uncovered the location of 'i-motifs' in a range of human cell lines. Using fluorescence techniques to pinpoint where the i-motifs were located, they identified numerous spots of green within the nucleus, which indicate the position of i-motifs.
"What excited us most is that we could see the green spots -- the i-motifs -- appearing and disappearing over time, so we know that they are forming, dissolving and forming again," says Dr Mahdi Zeraati, whose research underpins the study's findings.
The researchers showed that i-motifs mostly form at a particular point in the cell's 'life cycle' -- the late G1 phase, when DNA is being actively 'read'. They also showed that i-motifs appear in some promoter regions (areas of DNA that control whether genes are switched on or off) and in telomeres, 'end sections' of chromosomes that are important in the aging process.
Dr Zeraati says, "We think the coming and going of the i-motifs is a clue to what they do. It seems likely that they are there to help switch genes on or off, and to affect whether a gene is actively read or not."
"We also think the transient nature of the i-motifs explains why they have been so very difficult to track down in cells until now," adds A/Prof Christ.
A/Prof Marcel Dinger says, "It's exciting to uncover a whole new form of DNA in cells -- and these findings will set the stage for a whole new push to understand what this new DNA shape is really for, and whether it will impact on health and disease.”
研究人員證明，i-motif大多形成於細胞的“生命週期”中的特定時間點 - 後期的G1期，即DNA正在被“讀取”。 他們還表明，i圖案出現在一些啟動子區域（控制基因是否開啟或關閉的DNA區域）和端粒中，這些端粒是染色體的老化過程中重要的'末端部分'。 Zeraati博士說：“我們認為i圖案的來來往往是他們所做工作的線索，似乎他們可以幫助開啟或關閉基因，並影響基因是否被主動讀取“。
“我們也認為i圖案的短暫性質解釋了為什麼直到現在它們很難追踪細胞，”基督教教授補充道。A / Marcel Dinger教授表示：“發現細胞中一種全新的DNA形式令人興奮 - 這些發現將為全新推動了解這種新DNA形狀真正起作用以及它是否會影響DNA研究奠定基礎。關於健康和疾病“。
Source: Garvan Institute of Medical Research
In a world first, researchers have identified a new DNA structure -- called the i-motif -- inside cells. A twisted 'knot' of DNA, the i-motif has never before been directly seen inside living cells.
It's DNA, but not as we know it.
In a world first, Australian researchers have identified a new DNA structure -- called the i-motif -- inside cells. A twisted 'knot' of DNA, the i-motif has never before been directly seen inside living cells.
The new findings, from the Garvan Institute of Medical Research, are published today in the leading journal Nature Chemistry.
Deep inside the cells in our body lies our DNA. The information in the DNA code -- all 6 billion A, C, G and T letters -- provides precise instructions for how our bodies are built, and how they work.
The iconic 'double helix' shape of DNA has captured the public imagination since 1953, when James Watson and Francis Crick famously uncovered the structure of DNA. However, it's now known that short stretches of DNA can exist in other shapes, in the laboratory at least -- and scientists suspect that these different shapes might play an important role in how and when the DNA code is 'read'.
首先，澳大利亞的研究人員在細胞內發現了一種新的DNA結構 - 稱為i-基元。 一個扭曲的“DNA結”，i-motif以前從未在活細胞內直接看到過。
來自Garvan醫學研究所的新發現今天發表在主要期刊Nature Chemistry上 。
我們體內的細胞深處是我們的DNA。 DNA代碼中的信息 - 全部60億A，C， G和T字母 - 為我們的身體如何構建以及如何工作提供了精確的說明。
自1953年以來，詹姆斯沃森和弗朗西斯克里克著名揭開DNA的結構，標誌性的“雙螺旋”DNA形狀已經吸引了公眾的想像力。 然而，現在已知DNA短片段可以以其他形式存在，至少在實驗室中 - 科學家們懷疑這些不同的形狀可能在DNA代碼被讀取的時間和方式上發揮重要作用。新形狀與雙鏈DNA雙螺旋完全不同。
“當我們大多數人想到DNA時，我們會想到雙螺旋結構，”Daniel Christ副教授（加文公司抗體治療實驗室負責人）說。 “這項新研究提醒我們，存在完全不同的DNA結構 - 對我們的細胞很重要。”
The new shape looks entirely different to the double-stranded DNA double helix.
"When most of us think of DNA, we think of the double helix," says Associate Professor Daniel Christ (Head, Antibody Therapeutics Lab, Garvan) who co-led the research. "This new research reminds us that totally different DNA structures exist -- and could well be important for our cells."
"The i-motif is a four-stranded 'knot' of DNA," says Associate Professor Marcel Dinger (Head, Kinghorn Centre for Clinical Genomics, Garvan),.who co-led the research with A/Prof Christ.
"In the knot structure, C letters on the same strand of DNA bind to each other -- so this is very different from a double helix, where 'letters' on opposite strands recognise each other, and where Cs bind to Gs [guanines]."
Although researchers have seen the i-motif before and have studied it in detail, it has only been witnessed in vitro -- that is, under artificial conditions in the laboratory, and not inside cells.
雖然研究人員之前已經看到了i-motif並對其進行了詳細的研究，但它僅在體外見證過 - 即在實驗室的人工條件下，而不是在細胞內。事實上，這個領域的科學家們已經在討論是否所有活物內部都會存在i-motif“節點” - 這個問題由新發現解決了。
為了檢測細胞內的i圖案，研究人員開發了一種精確的新工具 - 抗體分子的片段 - 能夠以高親和力特異性識別並附著於i-圖案。 到目前為止，缺乏針對i圖案的抗體嚴重阻礙了他們對其作用的理解。
關鍵的是，抗體片段沒有檢測到螺旋形式的DNA，也沒有識別'G-四聯體結構'（一種結構相似的四鏈DNA排列）。
利用這一新工具，研究人員在一系列人類細胞系中發現了'i-motifs'的位置。 使用熒光技術來查明i圖案的位置，他們在細胞核內鑑定出許多綠色的斑點，這表明了i圖案的位置。
Mahdi Zeraati博士說：“最令我們激動的是，我們可以看到綠色的斑點 - 我的母題 - 隨著時間的推移而出現和消失，所以我們知道它們正在形成，溶解並再次形成，”他的研究支撐著研究結果。
In fact, scientists in the field have debated whether i-motif 'knots' would exist at all inside living things -- a question that is resolved by the new findings.
To detect the i-motifs inside cells, the researchers developed a precise new tool -- a fragment of an antibody molecule -- that could specifically recognise and attach to i-motifs with a very high affinity. Until now, the lack of an antibody that is specific for i-motifs has severely hampered the understanding of their role.
Crucially, the antibody fragment didn't detect DNA in helical form, nor did it recognise 'G-quadruplex structures' (a structurally similar four-stranded DNA arrangement).
With the new tool, researchers uncovered the location of 'i-motifs' in a range of human cell lines. Using fluorescence techniques to pinpoint where the i-motifs were located, they identified numerous spots of green within the nucleus, which indicate the position of i-motifs.
"What excited us most is that we could see the green spots -- the i-motifs -- appearing and disappearing over time, so we know that they are forming, dissolving and forming again," says Dr Mahdi Zeraati, whose research underpins the study's findings.
The researchers showed that i-motifs mostly form at a particular point in the cell's 'life cycle' -- the late G1 phase, when DNA is being actively 'read'. They also showed that i-motifs appear in some promoter regions (areas of DNA that control whether genes are switched on or off) and in telomeres, 'end sections' of chromosomes that are important in the aging process.
Dr Zeraati says, "We think the coming and going of the i-motifs is a clue to what they do. It seems likely that they are there to help switch genes on or off, and to affect whether a gene is actively read or not."
"We also think the transient nature of the i-motifs explains why they have been so very difficult to track down in cells until now," adds A/Prof Christ.
A/Prof Marcel Dinger says, "It's exciting to uncover a whole new form of DNA in cells -- and these findings will set the stage for a whole new push to understand what this new DNA shape is really for, and whether it will impact on health and disease.”
研究人員證明，i-motif大多形成於細胞的“生命週期”中的特定時間點 - 後期的G1期，即DNA正在被“讀取”。 他們還表明，i圖案出現在一些啟動子區域（控制基因是否開啟或關閉的DNA區域）和端粒中，這些端粒是染色體的老化過程中重要的'末端部分'。 Zeraati博士說：“我們認為i圖案的來來往往是他們所做工作的線索，似乎他們可以幫助開啟或關閉基因，並影響基因是否被主動讀取“。
“我們也認為i圖案的短暫性質解釋了為什麼直到現在它們很難追踪細胞，”基督教教授補充道。A / Marcel Dinger教授表示：“發現細胞中一種全新的DNA形式令人興奮 - 這些發現將為全新推動了解這種新DNA形狀真正起作用以及它是否會影響DNA研究奠定基礎。關於健康和疾病“。
Story Source:
Materials provided by Garvan Institute of Medical Research. Note: Content may be edited for style and length.
Materials provided by Garvan Institute of Medical Research. Note: Content may be edited for style and length.
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