加州大學(xué)戴維斯分校的科學(xué)家發(fā)現(xiàn),，一種在DNA拷貝方面起關(guān)鍵作用的蛋白同樣在修復(fù)裂口方面具有重要作用。這項(xiàng)研究有助于科學(xué)家理解癌細(xì)胞抑制輻射和化療的機(jī)制,，同樣有助于理解細(xì)胞如何在一開(kāi)始發(fā)生癌變。
一種能激增細(xì)胞核抗原的蛋白會(huì)形成了一個(gè)環(huán),，裝配在DNA雙螺旋結(jié)構(gòu)周圍,。該環(huán)有助于固定DNA聚合酶,。DNA聚合酶使得細(xì)胞在分裂成兩個(gè)新的細(xì)胞時(shí)能夠形成一個(gè)DNA鏈的拷貝。
這項(xiàng)研究結(jié)果發(fā)布在11月25日的Molecular Cell上,，表明在DNA重組中,，增殖細(xì)胞核抗原（PCNA）能執(zhí)行相似的功能。
研究人員開(kāi)發(fā)了一個(gè)系統(tǒng),，他們使用設(shè)計(jì)的DNA底物和純化蛋白,，在試管中檢測(cè)一些其他分子的行為,，這些分子同時(shí)包含在DNA拷貝和DNA修復(fù)中,。
Heyer的實(shí)驗(yàn)室開(kāi)始是使用酵母進(jìn)行實(shí)驗(yàn)的，但是酵母不能獲得癌癥,。但研究人員注意到,，酵母的DNA重組和修復(fù)機(jī)制和人類基本上是相同的。
放療和癌癥藥物同樣會(huì)使癌細(xì)胞DNA發(fā)生缺口,，過(guò)多的缺口可以使致命細(xì)胞死亡,。但是細(xì)胞修復(fù)裝置會(huì)修復(fù)裂口。
理解DNA重組和修復(fù)的機(jī)制,，為癌癥治療開(kāi)辟了一條新的道路,，使腫瘤更易于治療，或者預(yù)測(cè)病人對(duì)特定療法的效果,。這項(xiàng)研究同樣表明,，基因使得有些人更易受到癌癥影響。比如,，“乳腺癌基因”BRCA-2,，該基因參與DNA修復(fù)。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell, Volume 36, Issue 4, 704-713, 25 November 2009 doi:10.1016/j.molcel.2009.09.036
PCNA Is Required for Initiation of Recombination-Associated DNA Synthesis by DNA Polymerase δ
Xuan Li1, 4, Carrie M. Stith3, Peter M. Burgers3 and Wolf-Dietrich Heyer1, 2, ,
1 Department of Microbiology, University of California, Davis, Davis, CA 95616-8665, USA
2 Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616-8665, USA
3 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
Genetic recombination ensures proper chromosome segregation during meiosis and is essential for genome stability and tumor suppression. DNA synthesis after Rad51-mediated DNA strand invasion is a crucial step during recombination. PCNA is known as the processivity clamp for DNA polymerases. Here, we report the surprising observation that PCNA is specifically required to initiate recombination-associated DNA synthesis in the extension of the 3′ end of the invading strand in a D loop. We show using a reconstituted system of yeast Rad51, Rad54, RPA, PCNA, RFC, and DNA polymerase δ that loading of PCNA by RFC targets DNA polymerase δ to the D loop formed by Rad51 protein, allowing efficient utilization of the invading 3′ end and processive DNA synthesis. We conclude that PCNA has a specific role in the initiation of recombination-associated DNA synthesis and that DNA polymerase δ promotes recombination-associated DNA synthesis.
