癌癥治療新方案→ 阻斷堿性磷酸酶對(duì)DNA修復(fù)已閱

1、A research group in the Faculty of Medicine & Dentistry at the University of Alberta is hoping its latest discovery could one day be used to develop new therapies that target certain types of cancers .The discovery by Mark Glover, his graduate student Zahra Havali-Shahriari and post-doctoral fel

2、low Nicolas Coquelle has shed light on what happens in cells when DNA is damaged. They solved the structure of a DNA repair enzyme called polynucleotide kinase/phosphatase, or PNKP. This allows them to see what is happening when this enzyme is repairing DNA.Their findings have been published in the

3、Proceedings of the National Academy of Sciences, a high-impact scientific journal.In normal cells damaged DNA can lead to the breakdown of chromosomes and, ultimately, cancers. On the other hand, damaging DNA in cancer cells is a useful way to kill them. A long-term goal of this research is to find

4、ways to specifically block PNKP from doing its repair work in cancer cells as a possible new cancer therapy."We can finally visualize it bound to the damaged ends of DNA," said Glover, a professor in the Department of Biochemistry. "We've trappedthe enzyme bound to the damaged DNA

5、 before it actually repairs the damage. One of the surprising things that comes out of this study is that we also see that the enzyme has to unwind the DNA double helix."Work over the last 10 years, pioneered in large part in the Faculty of Medicine & Dentistry, revealed that the enzyme PNK

6、P plays a critical role in the repair of broken DNA ends produced by radiation and other agents. Until now, though, no one knew how it finds and repairs the damage."It breaks base pairs of DNA apart, peels off the broken end and then PNKP inserts that broken end into the enzyme," explains

7、Glover. "It then performs a chemical reaction on the damaged DNA end, reversing the damage and releasing it so that the broken DNA strand can be welded together with the rest of the double helix. We now understand more about how this thing works; an enzyme that is protecting us from getting can

8、cers."However, the same enzyme also protects cancer cells. "We find a lot of tumours become resistant to these therapies radiation and chemotherapy," said Glover. "The holy grail of cancer therapy is to find drugs that we could give to people that would sensitize their tumours to

9、these therapies."One way you could sensitize tumours is to target what they're using to repair damaged DNA. One of the ideas is that we could specifically inhibit this PNKP enzyme."Sensitizing the tumours to therapies could also lower side effects, adds Glover.The lab is already starti

10、ng to test some compounds that could act as inhibitors for PNKP in tumours and they've seen some positive early results.Because radiation is proven effective in some but not all cancers, new treatment avenues are necessary. Glover is playing a vital role in moving potential new treatment forward

11、."It requires a lot of basic research to find out what's going on in all these different cancers," he said.A research group in the Faculty of Medicine & Dentistry at the University of Alberta is hoping its latest discovery could one day be used to develop new therapies that target

12、certain types of cancers.阿爾伯塔大學(xué)醫(yī)學(xué)與牙科學(xué)系的一個(gè)研究組希望最新研究結(jié)果有朝一日能夠成 為某種腫瘤的新治療The discovery by Mark Glover, his graduate student Zahra Havali-Shahriari and post-doctoral fellow Nicolas Coquelle has shed light on what happens in cells when DNA is damaged. They solved the structure of a DNA repair enzyme calle

13、d polynucleotide kinase/phosphatase, or PNKP. This allows them to see what is happening when this enzyme is repairing DNA.Mark Glover 和 他的研 究生 Zahra Havali-Shahriari 以 及博士 后 Nicolas Coquelle 在研究當(dāng) DNA 受損時(shí)細(xì)胞如何變化時(shí)揭示了這一研究結(jié)果。 Their findings have been published in the Proceedings of the National Academy o

14、f Sciences, a high-impact scientific journal.他們的研究結(jié)果已經(jīng)刊出在高影響因子的科學(xué)雜志美國(guó)國(guó)家科學(xué)院院刊 。 In normal cells damaged DNA can lead to the breakdown ofchromosomes and, ultimately, cancers. On the other hand, damaging DNA in cancer cells is a useful way to kill them. A long-term goal of this research is to find ways

15、 to specifically block PNKP from doing its repair work in cancer cells as a possible new cancer therapy.正常細(xì)胞的 DNA 發(fā)生損傷可以導(dǎo)致染色體的分解,最終引起癌癥的發(fā)生。另一 方面,癌細(xì)胞中持續(xù)受損的 DNA 會(huì)殺死正常細(xì)胞。 這項(xiàng)研究的長(zhǎng)期目標(biāo)就是要 找到一種途徑可以特異性地阻止磷酸酶在癌細(xì)胞中的修復(fù)作用, 這可以作為腫瘤 治療的新方法。"We can finally visualize it bound to the damaged ends of DNA," s

16、aid Glover, a professor in the Department of Biochemistry. " We've trapped the enzyme bound to the damaged DNA before it actually repairs the damage. One of the surprising things that comes out of this study is that we also see that the enzyme has to unwind the DNA double helix."生物化學(xué)系的

17、 Glover 教授指出:我們能夠想象得到它注定是 DNA 損傷的最終 結(jié)局。 在它實(shí)際上修復(fù)損傷之前,我們把酶包裹在受損的 DNA 之上。緊接著令 人驚奇的現(xiàn)象出現(xiàn)了,我們看到酶可以解開(kāi) DNA 雙螺旋結(jié)構(gòu)。Work over the last 10 years, pioneered in large part in the Faculty of Medicine & Dentistry, revealed that the enzyme PNKP plays a criticalrole in the repair of broken DNA ends produced by ra

18、diation and other agents. Until now, though, no one knew how it finds and repairs the damage. 過(guò)去十年來(lái)， 作為醫(yī)學(xué)與牙科學(xué)系的大部分先驅(qū)者認(rèn)為磷酸酶由放射和其他因素 所引起的受損的 DNA 修復(fù)過(guò)程中發(fā)揮重要作用 "It breaks base pairs of DNA apart, peels off the broken end and then PNKP inserts that broken end into the enzyme," explains Glover. &

19、quot;It then performs a chemical reaction on the damaged DNA end, reversing the damage and releasing it so that the broken DNA strand can be welded together with the rest of the double helix. We now understand more about how this thing works; an enzyme that is protecting us from getting cancers.&quo

20、t; Glover 解釋?zhuān)核梢粤呀?DNA 堿基對(duì)，剝脫受損的末端，然后插入磷酸酶。 然后在受損的 DNA 末端發(fā)生化學(xué)反應(yīng)，逆轉(zhuǎn)損傷，并釋這一過(guò)程，這樣受損的 DNA 鏈既可以與剩余的雙螺旋結(jié)構(gòu)連接在一起?，F(xiàn)在，我們對(duì)這一工作原理有 了更多的了解，酶類(lèi)正在保護(hù)我們免受癌癥的侵襲。 However, the same enzyme also protects cancer cells. "We find a lot of tumours become resistant to these therapies radiation and chemotherapy," sai

21、d Glover. "The holy grail of cancer therapy is to find drugs that we could give to people that would sensitize their tumours to these therapies. 然而，相同的酶同時(shí)保護(hù)著癌細(xì)胞。Glover 解釋道：我們發(fā)現(xiàn)許多腫瘤對(duì)放療 及化療這些治療方法產(chǎn)生了耐受性。 腫瘤治療的黃金法則就是找到能夠使腫瘤對(duì) 治療方法產(chǎn)生敏感性的藥物。 "One way you could sensitize tumours is to target what they're using to repair damaged DNA. One of the ideas is that we could specifically inhibit this PNKP enzyme." 對(duì)腫瘤產(chǎn)生敏感性的一種方式就是以修復(fù)受損 DNA 的物質(zhì)為靶目標(biāo)。其中之一 就是我們能夠特異性地抑制磷酸酶。