Publication Date:
2012-02-11
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693633/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693633/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Jikui -- Teplova, Marianna -- Ishibe-Murakami, Satoko -- Patel, Dinshaw J -- P30 CA008748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):709-12. doi: 10.1126/science.1214453.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323818" target="_blank"〉PubMed〈/a〉
Keywords:
5-Methylcytosine/chemistry/metabolism
;
Animals
;
Base Pairing
;
Catalytic Domain
;
Crystallography, X-Ray
;
DNA/chemistry/*metabolism
;
DNA (Cytosine-5-)-Methyltransferase/*chemistry/genetics/*metabolism
;
*DNA Methylation
;
Dinucleoside Phosphates/chemistry
;
Hydrophobic and Hydrophilic Interactions
;
Mice
;
Models, Molecular
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Substrate Specificity
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
