法國國家科研中心9月3日宣布,，該中心與加拿大多倫多大學的研究人員共同發(fā)現(xiàn)了細胞在分裂過程中將自身信息傳遞給新細胞的機制，這一發(fā)現(xiàn)將有助于醫(yī)學界尋找治療癌癥的新方法,。
據(jù)科研中心介紹,，基因的表達能力與脫氧核糖核酸（DNA）的甲基化緊密相關(guān)，后者直接參與基因的表達和調(diào)控,，從而決定細胞的屬性和功能,。當一個細胞發(fā)生分裂時，它會把DNA的甲基化忠實地復制下來,，將信息傳遞給下一代的細胞,，在此過程中，一種名為UHRF1的蛋白質(zhì)起到了重要的作用,。
研究人員指出,，人體內(nèi)的部分基因能夠阻止癌細胞擴散，而后者會反過來抑制這些基因的表達,，并在分裂時將這種“本領(lǐng)”傳遞給新的癌細胞,。此外，科學家們在幾年前就注意到,，UHRF1在癌細胞中的含量很高,，他們認為，如果能夠研制出抑制這種蛋白質(zhì)作用的藥物,，那么將為癌癥的治療帶來新的希望,。
這一研究成果發(fā)表在最新一期英國《自然》（Nature）雜志網(wǎng)絡(luò)版上。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature,，doi:10.1038/nature07273,，George V. Avvakumov，Sirano Dhe-Paganon
Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1
George V. Avvakumov1,5, John R. Walker1,5, Sheng Xue1, Yanjun Li1, Shili Duan2, Christian Bronner3, Cheryl H. Arrowsmith1,2 & Sirano Dhe-Paganon1,4
Epigenetic inheritance in mammals is characterized by high-fidelity replication of CpG methylation patterns during development1, 2. UHRF1 (also known as ICBP90 in humans and Np95 in mouse)3 is an E3 ligase important for the maintenance of global and local DNA methylation in vivo4, 5. The preferential affinity of UHRF1 for hemi-methylated DNA over symmetrically methylated DNA by means of its SET and RING-associated (SRA) domain6 and its association with the maintenance DNA methyltransferase 1 (DNMT1) suggests a role in replication of the epigenetic code4, 5, 7. Here we report the 1.7 Å crystal structure of the apo SRA domain of human UHRF1 and a 2.2 Å structure of its complex with hemi-methylated DNA, revealing a previously unknown reading mechanism for methylated CpG sites (mCpG). The SRA–DNA complex has several notable structural features including a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. Two specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other three bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand. The structure, along with mutagenesis data, suggests how UHRF1 acts as a key factor for DNMT1 maintenance methylation through recognition of a fundamental unit of epigenetic inheritance, mCpG.
