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Scientists See DNA Get 'Sunburned' For The First Time

02/16/07 -- For the first time, scientists have observed DNA being damaged by ultraviolet (UV) light.

Ohio State University chemists and their colleagues in Germany used a special technique to watch strands of DNA in the laboratory sustain damage in real time.

They observed the most common chemical reaction among a family of reactions on the DNA molecule that are linked to sunburn, and discovered that this key reaction happens with astounding speed -- in less than one picosecond, or one millionth of one millionth of a second.

Scientists are studying UV damage to understand the role it plays in sunburn and diseases such as skin cancer. This new finding, reported in the current issue of the journal Science, shows that the damage depends greatly on the position of the DNA at the moment the UV strikes the molecule.

UV light excites the DNA molecule by adding energy, said Bern Kohler, associate professor of chemistry at Ohio State. Some exited energy states last a long time, and others a short time. The energy often decays away harmlessly, but occasionally it triggers a chemical reaction that alters the DNA's molecular structure.

Previously, scientists believed that the longer a DNA molecule was excited by UV energy, the greater the chance that it would sustain damage. So long-lived excited states were thought to be more dangerous than short-lived ones. But this study shows that the most common UV damage is caused by a very short-lived excited state.

"The speed of this reaction has important consequences for understanding how DNA is damaged by UV light," said Kohler. "In this study, we didn't see any evidence that long-lived energy states are responsible for damage. Now it seems more likely that short-lived states cause the most common chemical damage to DNA."

That damage consists of two tiny molecular bonds that form where they shouldn't -- between two thymine bases stacked together among the billions of bases in the DNA double helix.

DNA employs some chemical reactions of its own to heal itself. But when DNA sustains too much damage, it can't replicate properly. Badly damaged cells simply die -- the effect that gives sunburn its sting. Scientists also believe that chronic damage creates mutations that lead to diseases such as skin cancer.

For this study, the chemists used a technique called transient absorption to observe the DNA damage. Transient absorption is based on the idea that molecules absorb light at specific wavelengths, and it allows researchers to study events that happen in less than a picosecond.

They took specially designed strands of DNA -- ones made solely of thymine bases, in order to boost the chance of observing a reaction between adjacent thymines -- and exposed them to UV light. Then they timed the reactions that caused the new thymine bonds to form.

Kohler stressed that he and his colleagues examined damage to isolated DNA strands, not DNA within a cell. Sunburn results from a series of chemical reactions in a living cell, and so this experiment did not allow them to see a cell sustain sunburn.

This is, however, the first time anyone has observed the initial molecular events behind damage to DNA. Kohler thinks the results might make scientists attack the problem of UV damage in a new way.

DNA in a cell is always moving, he explained. It bends and twists one way or another because it is a relatively flexible molecule. This flexibility enables the normal chemical reactions that are constantly happening in the cell. Each shape-shift can require anywhere from a few to several hundred picoseconds to complete.

That's fast, but this new study shows that UV damage happens many times faster. On the timescale that the unwanted bonds form, even a rapidly moving DNA molecule would essentially appear frozen.

That means that whether or not two thymine bases are damaged depends on the position of the DNA during the extremely brief time required for it to absorb UV light. Either two thymine bases are lined up in just the right way to bond when the UV hits, or they're not.

"This insight explains why some pairs of thymine bases get damaged more frequently than others, and it suggests that scientists can understand damage patterns to DNA by studying the factors that influence how the bases are arranged in space," Kohler said.

"In our efforts to understand photo-damage, this new result shifts our attention to the DNA structure, and the kinds of arrangements that exist at the moment DNA absorbs light."
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2007年2月16日--科学家首次发现被晒伤的DNA
俄亥俄州大学化学家及其在德国的同事使用一种特殊的仪器在实验室实时地观察到持续地受到损伤DNA链。
他们观察到发生被晒伤的DNA分子上发生系列反应中最普遍的化学反应,并且发现这种反应速度惊人—至少以每皮秒或者每秒百万分之一的速度。
科学家研究紫外线损伤以了解晒伤和疾病如皮肤癌条件下其作用机制。发表在《科学》杂志的新的研究发现表明DNA损伤很大程度上依赖于在紫外线攻击DNA的时候DNA的位置。
俄亥俄州化学系副教授Bern Kohler说紫外线通过增加能量来激发DNA。一些激发态能量状态保持相当长的时间,另外一些可保持较短的时间。该能量通常自然消退对DNA不会造成伤害,但是偶尔它能激发化学反应改变DNA的结构。
学家以前认为DNA受紫外线激发的时间越长,DNA维持损伤的机会越多。长时间的激发状态被认为要比短期的激发态更危险。但是该研究表明最普通的紫外线损伤是由于时间非常短的激发态所导致。
“该反应的速度是理解DNA如何受紫外线伤害重要的原因,”在该研究中,我们没发现任何关于长期的能量状态是DNA受损伤的证据。现在看来最可能的是短期的能量状态引起最普通的DNA损伤。
该DNA损伤由两个胸腺嘧啶形成的两个小的分子间键组成,在该处这两个碱基不会在由成千上万个碱基组成的DNA双螺旋中堆积起来。
DNA使用一些化学反应来修复自己。但是当DNA遭受太大损伤时,它不能正确的复制。受到严重损伤的细胞以简单的方式死亡---晒伤产生的结果。科学家相信长期的损伤将产生基因突变可导致疾病例如皮肤癌。
就该项研究,科学家使用了一种被称作短暂吸收的技术观察DNA损伤。短暂吸收基于分子吸收特异波长的原理,这使得研究者研究发生反应非常快低于皮秒的事件。
他们设计采用了特异的DNA链—为了增加观察临近胸腺嘧啶反应,一条链仅由胸腺嘧啶组成,并且暴露于紫外光下。然后他们记录了产生新的胸腺嘧啶键形成的反应。
Kohler强调,他和他同事检测的DNA损伤是发生在离体的DNA,而不是细胞内的。晒伤是活细胞中由系列的化学反应产生的,因此,该项试验中他们并未观察到遭受晒伤的细胞。
然而,这也是人们首次观察到DNA受损伤后的启始分子事件。Kohler认为该研究结果或许帮助科学家使用新的方式来解决紫外线损伤问题。
他解释说细胞内DNA是动态的,由于具相对的弹性,它们以某种方式可以弯曲或者缠绕。这种弹性也使得在细胞内经常发生正常的化学反应。任何位置每种形态的改变过程需要几个或者几百个皮秒。
该反应速度非常快,但是新的研究也表明紫外线损伤以更快的速度可发生多次。在不必要的键形成的标量时间中,即使快速移动的DNA分子也必须要凝固。
这就意味者无论两个胸腺嘧啶是否受到损伤都要依赖于在吸收紫外线极端短的时间内DNA的位置。当受到紫外线伤害的时候,胸腺嘧啶或者线性排列以正确的方式形成键或者不产生键。
“该新见解可以为什么一些配对的解释胸腺嘧啶要比其他的容易受到损伤,这也表明科学家们通过研究一些因素是如何影响空间上碱基的排列来理解DNA损伤模式。”Kohler说。
“在我们努力研究光损伤的过程中,这项新的研究结果使我们关注点转移到DNA结构上来,DNA吸收光时可产生不同的排列方式。
来自:俄亥俄州大学
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