近日,，國際著名雜志Science在線刊登了國外研究人員的最新研究成果“Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA Methylation”，文章中,，作者對基因沉默進行了結(jié)構(gòu)性闡釋,。
一項新的研究闡釋了DNA與維持DNA甲基化的酶之間的相互作用,；DNA甲基化是一個過程,，在該過程中，DNA的化學變化影響甚至可令某個基因的表達沉默,。 在整個細胞世代中,，某些甲基化模式的維持是由酶DNMT1完成的。
Jikui Song及其同事已經(jīng)確定了小鼠的與DNA雙鏈體結(jié)合的 DNMT1的晶體結(jié)構(gòu),，該雙鏈體的親代鏈上含有在DNA剛復(fù)制之后可被發(fā)現(xiàn)的某個部分甲基化的部位,。 這些結(jié)果顯示了 DNMT1是如何將DNA的標靶胞嘧啶堿基快速翻轉(zhuǎn)到該酶的催化袋中的。（生物谷Bioon.com）
doi:10.1126/science.1214453
PMC:
PMID:
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
