在活的人类细胞中发现的神秘的新DNA结构


An artist's impression of the i-motif DNA structure inside cells,along with the antibody-based tool used to detect it. Chris Hammang

大约65年前,杰姆斯DWatson and Francis H.C.克里克做出了一个启示性的发现。"We have found the secret of life!" Crickblurted out在酒吧里,Watson would later claim,after the pair mapped the famous double helix structure of DNA.

现在科学家发现“生命的秘密”—DNA– hosts another kind of structure.除了双股螺旋,a four-stranded tangle,known as an i-motif,has been shown to exist throughout our genetic material.Its detection within human cells suggests it occurs naturally and may carry a biological role that could be targeted to treat diseases such ascancer.

"People had already shown that you can form these i-motif structures in the test tube using laboratory techniques," says Daniel Christ,head of antibody therapeutics at the Garvan Institute of Medical Research in Australia and co-author of a学习about the DNA structures published April 23 in Nature Chemistry.但最突出的是这些结构确实存在于活的人类细胞中。这就是我们现在所展示的,这意味着我们的细胞中存在着完全不同的DNA结构。”

Flourescent Tracking

In the new study,Christ and his Garvan Institute colleagues,Mahdi Zeraati and Marcel Dinger,developed an antibody fragment that specifically seeks out and binds to i-motifs.The antibody was equipped with a biological marker that glows under fluorescent light.这种方式,the team was able to map where i-motifs were located by identifying fluorescent markers in cells' nuclei.

The method,耶稣基督说:真正的“移动酒吧”,以促进我们对i-主题的理解,因为知道它们发生在哪里可以提供线索,他们可能正在做什么。人类DNA是巧妙包装的奇迹。If the DNA from one cell were stretched out,it would extend for about six and a half feet (about 2 meters).把30亿对碱基塞进6微米(0.0002英寸)的空间的必要性意味着遗传物质以复杂的模式排列和折叠。

An illustration of an i-motif embedded in a strand of DNA.
马哈迪泽拉蒂

Within this intricate packing,the double-helix structure dominates,but,Christ说他的团队发现i基序结构“相当普遍”,虽然他们还不能估计DNA中i基序的实际数量,they likely number in the 10,000s within each genome,丁格在一封电子邮件中说。They're also "dynamic," meaning they can fold and unfold,depending on conditions.

The structures are primarily made up of cytosines,one of the four main bases found in DNA (and RNA),along with adenine,guanine and thymine.通常,胞嘧啶与DNA双螺旋结构的鸟嘌呤结合,but in i-motifs,cytosines bind to each other to form an off-shoot from the double helix.

这种奇怪的结构似乎也有利于酸性条件。These are the kinds of conditions in which i-motifs had previously been detected during laboratory experiments in the 1990s,and the latest research found that the structures' prevalence increases within the human cell when the environment is made more acidic.

So why do the structures exist?科学家还不确定,but some factors suggest they may play a role in regulating gene production.One reason is that i-motifs occur primarily "upstream" from where genes are made in the DNA structure,according to Randy Wadkins,密西西比大学化学和生物化学教授,没有参与这项研究。

"We have some 30,000 genes in the human genome but they're not made all the time — it's not a continuous process," Wadkins explains.这些可能是一种机制,就像基因形成初期的刻度盘一样,决定你是制造了一点点还是大量的基因。i-motifs通常位于像这样的拨号盘所在的位置。”

可能与癌症有关

沃金斯的实验室一直在研究i基序在癌症中的可能作用。癌细胞的问题是它们繁殖迅速,而且生长不受控制。If the i-motif structure plays a role in regulating genes that signal a tumor's growth,然后,它可能会为未来阻止癌症扩散的治疗提供一个目标。

"If you could find a small molecule that interacts with i-motif alone,then you might be able to regulate the formation of,say,tumor cells," Wadkins says,adding that for now this is just speculation.

The immediate next step will be to confirm the Australian team's findings and then dig into the specifics and functions of these novel DNA structures.正如丁格所说,科学家们刚刚开始了解人类DNA的所有形式和功能。

"We can only interpret about 2 percent of the human genome," says Dinger."The function of most of it remains a mystery – the discovery of the i-motif adds a new lens through which we can look at the genome and understand how it works."