研究人員早已注意到,，人體中缺乏一種多數(shù)動(dòng)物甚至植物帶有的能夠修復(fù)嚴(yán)重太陽(yáng)灼傷的酶。美國(guó)俄亥俄州立大學(xué)的科學(xué)家在《自然》（Nature）雜志網(wǎng)站上撰文表示,，他們首次觀察到了這種酶是如何修復(fù)受損DNA的,。該發(fā)現(xiàn)有望幫助人們開(kāi)發(fā)新的曬傷療法和皮膚癌預(yù)防方法。
俄亥俄州立大學(xué)物理學(xué)家和化學(xué)家仲東平與同事介紹說(shuō),，他們觀察到光解酶（photolyase）向受損的DNA鏈注射一個(gè)電子和一個(gè)質(zhì)子,、在10億分之?dāng)?shù)秒內(nèi)修復(fù)損傷的情況。仲東平表示,，這聽(tīng)起來(lái)簡(jiǎn)單,，但實(shí)際上電子和質(zhì)子注入后產(chǎn)生了一系列非常復(fù)雜的化學(xué)反應(yīng)。這一切雖然發(fā)生在瞬間,，時(shí)機(jī)卻十分恰當(dāng),。
在實(shí)驗(yàn)中，仲東平他們將自己合成的DNA放在紫外線下照射,，讓DNA出現(xiàn)類(lèi)似于曬傷的損傷,，然后加入光解酶，并用超快光脈沖成像技術(shù)獲得了揭示光解酶修復(fù)受損DNA過(guò)程的系列圖片,。
紫外線導(dǎo)致人類(lèi)患上皮膚癌的原因是它使得細(xì)胞中沿著DNA分子不正確的地方出現(xiàn)了化學(xué)鍵,。仲東平的研究顯示，光解酶能夠解散這些錯(cuò)誤的化學(xué)鍵,，讓DNA的原子重新回到原來(lái)的位置,。同時(shí)，他們還發(fā)現(xiàn),，修復(fù)完成后,，DNA螺旋鏈會(huì)自動(dòng)向光解酶發(fā)射出電子和質(zhì)子，這讓光解酶能繼續(xù)修復(fù)其他受損的DNA,。
人類(lèi)被陽(yáng)光曬傷后,，其體內(nèi)的酶沒(méi)有能力修復(fù)DNA損傷，皮膚細(xì)胞出現(xiàn)死亡,?？茖W(xué)家將慢性皮膚曬傷同DNA變異聯(lián)系起來(lái),，認(rèn)為DNA變異導(dǎo)致了諸如皮膚癌等疾病。仲東平表示,，現(xiàn)在人們認(rèn)識(shí)了光解酶的作用機(jī)理,，有望利用該信息設(shè)計(jì)出治療陽(yáng)光曬傷的藥物或皮膚霜。
科學(xué)家表示,，常見(jiàn)的防曬霜的作用是將紫外線轉(zhuǎn)變成熱能或反射紫外光,。含有光解酶的防曬霜?jiǎng)t有可能治療穿透進(jìn)皮膚的紫外線所引起的損害。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature09192
Dynamics and mechanism of repair of ultraviolet-induced (6–4) photoproduct by photolyase
Jiang Li1, Zheyun Liu1, Chuang Tan1, Xunmin Guo1, Lijuan Wang1, Aziz Sancar2 & Dongping Zhong1
1 Departments of Physics, Chemistry and Biochemistry, Programs of Biophysics, Chemical Physics and Biochemistry, 191 West Woodruff Avenue, The Ohio State University, Columbus, Ohio 43210, USA
2 Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
One of the detrimental effects of ultraviolet radiation on DNA is the formation of the (6–4) photoproduct, 6–4PP, between two adjacent pyrimidine rings1. This lesion interferes with replication and transcription, and may result in mutation and cell death2. In many organisms, a flavoenzyme called photolyase uses blue light energy to repair the 6–4PP (ref. 3). The molecular mechanism of the repair reaction is poorly understood. Here, we use ultrafast spectroscopy to show that the key step in the repair photocycle is a cyclic proton transfer between the enzyme and the substrate. By femtosecond synchronization of the enzymatic dynamics with the repair function, we followed the function evolution and observed direct electron transfer from the excited flavin cofactor to the 6–4PP in 225?picoseconds, but surprisingly fast back electron transfer in 50?picoseconds without repair. We found that the catalytic proton transfer between a histidine residue in the active site and the 6–4PP, induced by the initial photoinduced electron transfer from the excited flavin cofactor to 6–4PP, occurs in 425?picoseconds and leads to 6–4PP repair in tens of nanoseconds. These key dynamics define the repair photocycle and explain the underlying molecular mechanism of the enzyme’s modest efficiency.
