DNA復(fù)制是活體生物的基本生命過(guò)程,，允許細(xì)胞進(jìn)行分裂和增殖，并維持原始細(xì)胞的遺傳編碼和適當(dāng)功能,。對(duì)于該過(guò)程或機(jī)制的理解,，也出現(xiàn)了很多挑戰(zhàn)，比如雙螺旋的DNA分離成兩個(gè)股鏈后,，這兩股鏈會(huì)用不同的方式進(jìn)行復(fù)制,，然而卻能同時(shí)完成復(fù)制,。
根據(jù)12月17日Nature上的一篇文章，在一項(xiàng)由美國(guó)羅伯特伍德約翰遜醫(yī)學(xué)院和伊利諾斯大學(xué)共同完成的研究中,，科學(xué)家關(guān)注了上述重要的問(wèn)題,。研究識(shí)別了3種重要的方式，解答了科學(xué)家關(guān)于DNA雙鏈同時(shí)完成拷貝的疑問(wèn),。
DNA復(fù)制是一個(gè)重要的過(guò)程,，對(duì)于活細(xì)胞的生存和增殖來(lái)說(shuō)是必須的。這同樣也是一個(gè)已經(jīng)被研究了十幾年的復(fù)雜問(wèn)題,，但是對(duì)于兩條鏈同時(shí)完成拷貝的機(jī)制還不是很清楚,。Smita Patel教授介紹說(shuō)，這項(xiàng)研究解釋了復(fù)制過(guò)程是如何協(xié)調(diào)完成的,，DNA復(fù)制錯(cuò)誤能夠?qū)е聶C(jī)體缺陷和疾病,，比如癌癥。
解旋酶啟動(dòng)DNA復(fù)制,，然后通過(guò)DNA聚合酶雙鏈會(huì)重新生成,。一條鏈叫前導(dǎo)鏈會(huì)連續(xù)不斷的再生，另一條鏈?zhǔn)请S從鏈,，通過(guò)片段連接重新產(chǎn)生,。
研究人員使用state-of-the-art方法在毫秒水平測(cè)量DNA合成的過(guò)程。研究表明,，短片段是以很快的速率合成的,，因此隨從鏈的合成能夠和前導(dǎo)鏈的合成保持一致。
研究人員捕獲了DNA生成過(guò)程中的復(fù)制酶,，識(shí)別了3種DNA雙鏈同時(shí)完成復(fù)制的方式,。研究人員注意到，隨從鏈的聚合酶會(huì)以更快的速度跟隨著前導(dǎo)鏈的聚合酶,，這就給隨從鏈聚合酶額外的時(shí)間重新開(kāi)始新片段的生成,。這項(xiàng)發(fā)現(xiàn)也支持了先前由加利福尼亞大學(xué)生化教授Bruce Alberts提出的模型。
此外,，研究人員表示,，根據(jù)RNA引物的產(chǎn)生過(guò)程，復(fù)制的時(shí)間將進(jìn)一步縮減,。因此,，隨從鏈合成酶的快速移動(dòng)，使得RNA引物產(chǎn)生提前,，聚合酶能夠快速捕獲RNA引物,，使得雙鏈能夠同時(shí)完成復(fù)制。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 462, 940-943 (17 December 2009) | doi:10.1038/nature08611
Coordinating DNA replication by means of priming loop and differential synthesis rate
Manjula Pandey1, Salman Syed2, Ilker Donmez1, Gayatri Patel1, Taekjip Ha2,3 & Smita S. Patel1
1 Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
2 Howard Hughes Medical Institute, Urbana, Illinois 61801, USA
3 Department of Physics and the Center for the Physics of Living Cells, University of Illinois, Urbana-Champaign, Illinois 61801, USA
Genomic DNA is replicated by two DNA polymerase molecules, one of which works in close association with the helicase to copy the leading-strand template in a continuous manner while the second copies the already unwound lagging-strand template in a discontinuous manner through the synthesis of Okazaki fragments1, 2. Considering that the lagging-strand polymerase has to recycle after the completion of every Okazaki fragment through the slow steps of primer synthesis and hand-off to the polymerase3, 4, 5, it is not understood how the two strands are synthesized with the same net rate6, 7, 8, 9. Here we show, using the T7 replication proteins10, 11, that RNA primers are made ‘on the fly’ during ongoing DNA synthesis and that the leading-strand T7 replisome does not pause during primer synthesis, contrary to previous reports12, 13. Instead, the leading-strand polymerase remains limited by the speed of the helicase14; it therefore synthesizes DNA more slowly than the lagging-strand polymerase. We show that the primase–helicase T7?gp4 maintains contact with the priming sequence during ongoing DNA synthesis; the nascent lagging-strand template therefore organizes into a priming loop that keeps the primer in physical proximity to the replication complex. Our findings provide three synergistic mechanisms of coordination: first, primers are made concomitantly with DNA synthesis; second, the priming loop ensures efficient primer use and hand-off to the polymerase; and third, the lagging-strand polymerase copies DNA faster, which allows it to keep up with leading-strand DNA synthesis overall.
