Study of maintenance DNA methylation based on the structure of DNA methyltransferase

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: SUETAKE Isao 大阪大学, たんぱく質研究所, 准教授 (80304054)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Dnmt / DNA methylation / epigenetics

Outline of Final Research Achievements

DNA methylation of cytosine is a key epigenetic modification and crucial for normal development of mammals. DNA methylation patterns were maintained by Dnmt1. Mouse Dnmt1 is composed from multiple domains; the replication foci targeting sequence (RFTS), catalytic domain, and so on. From three-dimensional structure of mouse Dnmt1 lacking the N-terminal platform domain, a striking feature that the RFTS plugs the catalytic pocket is observed. Substrate DNA cannot gain access to the catalytic center unless the RFTS is removed from the catalytic pocket. Uhrf1 is reported to be a prerequisite factor. The SRA domain of Uhrf1 specifically recognizes hemi-methylated CpG.
In the present study, I have demonstrated that the direct interaction between the SRA of Uhrf1 and Dnmt1 contributes to the removal of the RFTS from the catalytic pocket to allow access of the substrate hemi-methylated DNA to the catalytic center. I elucidated one of the mechanisms to regulate maintenance methylation.

Free Research Field

生化学