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Science:基因沉默的结构性阐释

来源:EurekAlert 2012-02-10 14:25

近日,国际著名杂志Science在线刊登了国外研究人员的最新研究成果“Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA Methylation”,文章中,作者对基因沉默进行了结构性阐释。

一项新的研究阐释了DNA与维持DNA甲基化的酶之间的相互作用;DNA甲基化是一个过程,在该过程中,DNA的化学变化影响甚至可令某个基因的表达沉默。 在整个细胞世代中,某些甲基化模式的维持是由酶DNMT1完成的。

Jikui Song及其同事已经确定了小鼠的与DNA双链体结合的 DNMT1的晶体结构,该双链体的亲代链上含有在DNA刚复制之后可被发现的某个部分甲基化的部位。 这些结果显示了 DNMT1是如何将DNA的标靶胞嘧啶碱基快速翻转到该酶的催化袋中的。(生物谷Bioon.com)

Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA Methylation

Jikui Song*, Marianna Teplova, Satoko Ishibe-Murakami, Dinshaw J. Patel†

DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation. We report on the crystal structure of a productive covalent mouse DNMT1(731-1602)–DNA complex containing a central hemimethylated CpG site. The methyl group of methylcytosine is positioned within a shallow hydrophobic concave surface, whereas the cytosine on the target strand is looped out and covalently anchored within the catalytic pocket. The DNA is distorted at the hemimethylated CpG step, with side chains from catalytic and recognition loops inserting through both grooves to fill an intercalation-type cavity associated with a dual base flip-out on partner strands. Structural and biochemical data establish how a combination of active and autoinhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance DNA methylation.

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