法国国家科研中心9月3日宣布，该中心与加拿大多伦多大学的研究人员共同发现了细胞在分裂过程中将自身信息传递给新细胞的机制，这一发现将有助于医学界寻找治疗癌症的新方法。
据科研中心介绍，基因的表达能力与脱氧核糖核酸（DNA）的甲基化紧密相关，后者直接参与基因的表达和调控，从而决定细胞的属性和功能。当一个细胞发生分裂时，它会把DNA的甲基化忠实地复制下来，将信息传递给下一代的细胞，在此过程中，一种名为UHRF1的蛋白质起到了重要的作用。
研究人员指出，人体内的部分基因能够阻止癌细胞扩散，而后者会反过来抑制这些基因的表达，并在分裂时将这种“本领”传递给新的癌细胞。此外，科学家们在几年前就注意到，UHRF1在癌细胞中的含量很高，他们认为，如果能够研制出抑制这种蛋白质作用的药物，那么将为癌症的治疗带来新的希望。
这一研究成果发表在最新一期英国《自然》（Nature）杂志网络版上。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
