近日，上海交通大學(xué)鄧子新院士團(tuán)隊(duì)對(duì)DNA骨架硫修飾生物學(xué)意義的研究又獲得兩項(xiàng)突破,。聚焦核酸研究的著名國(guó)際學(xué)術(shù)刊物 Nucleic Acids Research 以特寫文章（Featured article）發(fā)表了由該團(tuán)隊(duì)德林副教授主持,，博士生徐鐵剛和姚芬為共同第一作者的論文——“沙門氏菌中與DNA骨架上硫修飾直接關(guān)聯(lián)的一種新的限制系統(tǒng)”,。該論文報(bào)道了一種新的宿主專一性限制-修飾系統(tǒng)，它與以前所熟知的DNA甲基化限制-修飾系統(tǒng)截然不同,，由7個(gè)基因負(fù)責(zé),，其功能與DNA骨架上的硫修飾直接相關(guān),。編輯部在特寫中寫道：“在沙門氏菌中所發(fā)現(xiàn)的這種宿主專一性硫修飾系統(tǒng)看來是細(xì)菌為了抵御外源對(duì)DNA的限制性所裝備的又一種新的細(xì)胞防衛(wèi)機(jī)制，它被一種新的途徑酶所編碼,，堪比細(xì)菌在依賴于DNA甲基化之外加裝了又一套新的防御體系”,。
與之相反的另一套全新的細(xì)胞防衛(wèi)系統(tǒng)發(fā)現(xiàn)于天藍(lán)色鏈霉菌中，由賀新義副教授主持,，博士生劉光為第一作者,，以“一種IV型限制內(nèi)切酶ScoMcrA對(duì)硫修飾和甲基化修飾DNA都切割”為題發(fā)表在 PLoS Genetics 上，這種酶不僅可以切割DNA骨架上發(fā)生了硫修飾的DNA,，還可以切割DNA堿基上發(fā)生了甲基化修飾的DNA,。另外，這套限制-修飾系統(tǒng)分別位于兩個(gè)相互排斥的基因組島上,，具有“水火不容”的敵對(duì)性,，兩者同時(shí)表達(dá)會(huì)導(dǎo)致細(xì)胞瞬時(shí)死亡。論文評(píng)審員稱這是一篇“重要的,、epoch-making”的論文,。這項(xiàng)發(fā)現(xiàn)是上海交大與中國(guó)科學(xué)院微生物研究所和英國(guó)Leicester大學(xué)合作的結(jié)晶。
這是鄧子新院士團(tuán)隊(duì)發(fā)現(xiàn)DNA骨架硫修飾以來,，瞄準(zhǔn)科技界普遍關(guān)注的有關(guān)DNA硫修飾的生物學(xué),，尤其是修飾的生理功能這個(gè)重大的科學(xué)問題公開發(fā)表的新的引人注目的原創(chuàng)性成果，充分顯示了我國(guó)在此前沿新興領(lǐng)域持之以恒的開拓性和創(chuàng)新性,。與DNA甲基化限制-修飾系統(tǒng)一樣,，這類新系統(tǒng)的廣泛和深度挖掘可能具有重大的分子生物學(xué)和生物工程學(xué)意義。
目前,，DNA骨架硫修飾的研究已成為該團(tuán)隊(duì)瞄準(zhǔn)前沿，奮力開拓的主要科研方向之一,，自他們首次報(bào)道DNA硫修飾以來,，已先后發(fā)表了十余篇相關(guān)的系統(tǒng)性研究論文，穩(wěn)步地把對(duì)此新興領(lǐng)域的研究推向新的高度,。
據(jù)悉,，2010年初，中國(guó)微生物學(xué)會(huì)為了促進(jìn),、激勵(lì)和紀(jì)念DNA硫修飾這個(gè)原創(chuàng)性科學(xué)發(fā)現(xiàn),，彰顯我國(guó)基礎(chǔ)生命科學(xué)領(lǐng)域的顯示度和影響力，決定在上海交通大學(xué)設(shè)立“DNA大分子硫修飾科學(xué)發(fā)現(xiàn)誕生地”紀(jì)念牌,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nucl. Acids Res. doi: 10.1093/nar/gkq610
A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella
Tiegang Xu, Fen Yao, Xiufen Zhou, Zixin Deng* and Delin You*
Abstract
A novel, site-specific, DNA backbone S-modification (phosphorothioation) has been discovered, but its in vivo function(s) have remained obscure. Here, we report that the enteropathogenic Salmonella enterica serovar Cerro 87, which possesses S-modified DNA, restricts DNA isolated from Escherichia coli, while protecting its own DNA by site-specific phosphorothioation. A cloned 15-kb gene cluster from S. enterica conferred both host-specific restriction and DNA S-modification on E. coli. Mutational analysis of the gene cluster proved unambiguously that the S-modification prevented host-specific restriction specified by the same gene cluster. Restriction activity required three genes in addition to at least four contiguous genes necessary for DNA S-modification. This functional overlap ensures that restriction of heterologous DNA occurs only when the host DNA is protected by phosphorothioation. Meanwhile, this novel type of host-specific restriction and modification system was identified in many diverse bacteria. As in the case of methylation-specific restriction systems, targeted inactivation of this gene cluster should facilitate genetic manipulation of these bacteria, as we demonstrate in Salmonella.
PLoS Genet. doi:10.1371/journal.pgen.1001253
Cleavage of Phosphorothioated DNA and Methylated DNA by the Type IV Restriction Endonuclease ScoMcrA
Guang Liu1, Hong-Yu Ou1, Tao Wang1, Li Li1, Huarong Tan2, Xiufen Zhou1, Kumar Rajakumar3,4, Zixin Deng1*, Xinyi He1*
1 Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China, 2 State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, 3 Department of Infection, Immunity, and Inflammation, Leicester Medical School, University of Leicester, Leicester, United Kingdom, 4 Department of Clinical Microbiology, University Hospitals of Leicester National Health Service Trust, Leicester, United Kingdom
Abstract
Many taxonomically diverse prokaryotes enzymatically modify their DNA by replacing a non-bridging oxygen with a sulfur atom at specific sequences. The biological implications of this DNA S-modification (phosphorothioation) were unknown. We observed that simultaneous expression of the dndA-E gene cluster from Streptomyces lividans 66, which is responsible for the DNA S-modification, and the putative Streptomyces coelicolor A(3)2 Type IV methyl-dependent restriction endonuclease ScoA3McrA (Sco4631) leads to cell death in the same host. A His-tagged derivative of ScoA3McrA cleaved S-modified DNA and also Dcm-methylated DNA in vitro near the respective modification sites. Double-strand cleavage occurred 16–28 nucleotides away from the phosphorothioate links. DNase I footprinting demonstrated binding of ScoA3McrA to the Dcm methylation site, but no clear binding could be detected at the S-modified site under cleavage conditions. This is the first report of in vitro endonuclease activity of a McrA homologue and also the first demonstration of an enzyme that specifically cleaves S-modified DNA.
