Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation Journal Article
| Authors: | Song, J.; Teplova, M.; Ishibe-Murakami, S.; Patel, D. J. |
| Article Title: | Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation |
| Abstract: | 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. |
| Keywords: | methylation; nonhuman; dna replication; protein conformation; chromosome; animals; mice; gene expression; enzyme activity; inhibitor; dna methylation; animalia; dna; double stranded dna; cpg island; substrate specificity; molecular analysis; genome; base pairing; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; rodent; catalysis; structure analysis; biochemistry; catalytic domain; protein structure, secondary; dna methyltransferase 1; dna (cytosine-5-)-methyltransferase; 5 methylcytosine; 5-methylcytosine; intercalation complex; hydrophobic and hydrophilic interactions; methyl group; dna protein complex; cytosine; covalent bond; hydrophobicity; dinucleoside phosphates; nitrogen compound |
| Journal Title: | Science |
| Volume: | 335 |
| Issue: | 6069 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2012-02-10 |
| Start Page: | 709 |
| End Page: | 712 |
| Language: | English |
| DOI: | 10.1126/science.1214453 |
| PROVIDER: | scopus |
| PUBMED: | 22323818 |
| PMCID: | PMC4693633 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "CODEN: SCIEA" - "Source: Scopus" |
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