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A. Jeltsch, T. Lanio (2002)
Site-directed mutagenesis by polymerase chain reaction.Methods in molecular biology, 182
R. Jurkowska, T. Jurkowski, A. Jeltsch (2011)
Structure and Function of Mammalian DNA MethyltransferasesChemBioChem, 12
Xiaoli Liu, Qinqin Gao, Pishun Li, Qian Zhao, Jiqin Zhang, Jiwen Li, H. Koseki, J. Wong (2013)
UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9Nature Communications, 4
S. Feng, S. Jacobsen, W. Reik (2010)
Epigenetic Reprogramming in Plant and Animal DevelopmentScience, 330
Ahmet Berkyurek, I. Suetake, K. Arita, K. Takeshita, A. Nakagawa, M. Shirakawa, S. Tajima (2013)
The DNA Methyltransferase Dnmt1 Directly Interacts with the SET and RING Finger-associated (SRA) Domain of the Multifunctional Protein Uhrf1 to Facilitate Accession of the Catalytic Center to Hemi-methylated DNA*The Journal of Biological Chemistry, 289
Ina Rhee, K. Bachman, B. Park, K. Jair, R. Yen, Kornel Schuebel, H. Cui, A. Feinberg, C. Lengauer, K. Kinzler, S. Baylin, B. Vogelstein (2002)
DNMT1 and DNMT3b cooperate to silence genes in human cancer cellsNature, 416
M. Bostick, Jong Kim, P. Estève, Amander Clark, S. Pradhan, S. Jacobsen (2007)
UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian CellsScience, 317
R. Klose, A. Bird (2006)
Genomic DNA methylation: the mark and its mediators.Trends in biochemical sciences, 31 2
Choel Kim, D. Vigil, G. Anand, Susan Taylor (2006)
Structure and dynamics of PKA signaling proteins.European journal of cell biology, 85 7
Angela Boettcher, Jian Wu, Choel Kim, Jie Yang, J. Bruystens, Nikki Cheung, Juniper Pennypacker, D. Blumenthal, A. Kornev, Susan Taylor (2011)
Realizing the allosteric potential of the tetrameric protein kinase A RIα holoenzyme.Structure, 19 2
R. Goyal, R. Reinhardt, A. Jeltsch (2006)
Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferaseNucleic Acids Research, 34
Y. Bergman, H. Cedar (2013)
DNA methylation dynamics in health and diseaseNature Structural &Molecular Biology, 20
Andrea Hermann, R. Goyal, A. Jeltsch (2004)
The Dnmt1 DNA-(cytosine-C5)-methyltransferase Methylates DNA Processively with High Preference for Hemimethylated Target Sites*Journal of Biological Chemistry, 279
A. Siddique, Suneetha Nunna, A. Rajavelu, Yingying Zhang, R. Jurkowska, R. Reinhardt, M. Rots, S. Ragozin, T. Jurkowski, A. Jeltsch (2013)
Targeted methylation and gene silencing of VEGF-A in human cells by using a designed Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity.Journal of molecular biology, 425 3
Julie Law, S. Jacobsen (2010)
Establishing, maintaining and modifying DNA methylation patterns in plants and animalsNature Reviews Genetics, 11
G. Egger, Shinwu Jeong, Sonia Escobar, C. Cortez, Tony Li, Yoshimasa Saito, C. Yoo, Peter Jones, G. Liang (2006)
Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survivalProceedings of the National Academy of Sciences, 103
Stefan Schiesser, T. Pfaffeneder, K. Sadeghian, Benjamin Hackner, B. Steigenberger, A. Schröder, J. Steinbacher, Gengo Kashiwazaki, G. Höfner, K. Wanner, C. Ochsenfeld, T. Carell (2013)
Deamination, oxidation, and C-C bond cleavage reactivity of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine.Journal of the American Chemical Society, 135 39
P. Bashtrykov, G. Jankevicius, Anita Smarandache, R. Jurkowska, S. Ragozin, A. Jeltsch (2012)
Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain.Chemistry & biology, 19 5
M. Fatemi, Andrea Hermann, Shriharsa Pradhan, A. Jeltsch (2001)
The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.Journal of molecular biology, 309 5
S. Pradhan, A. Bacolla, R. Wells, R. Roberts (1999)
Recombinant Human DNA (Cytosine-5) MethyltransferaseThe Journal of Biological Chemistry, 274
F. Syeda, Rebecca Fagan, Matthew Wean, G. Avvakumov, J. Walker, S. Xue, S. Dhe-Paganon, C. Brenner (2011)
The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1*The Journal of Biological Chemistry, 286
Jikui Song, O. Rechkoblit, T. Bestor, D. Patel (2011)
Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA MethylationScience, 331
A. Jeltsch (2002)
Beyond Watson and Crick: DNA Methylation and Molecular Enzymology of DNA MethyltransferasesChemBioChem, 3
P. Bashtrykov, S. Ragozin, A. Jeltsch (2012)
Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferaseFEBS Letters, 586
J. Sharif, M. Muto, S. Takebayashi, I. Suetake, A. Iwamatsu, T. Endo, J. Shinga, Y. Mizutani-Koseki, Tetsuro Toyoda, K. Okamura, S. Tajima, K. Mitsuya, M. Okano, H. Koseki (2007)
The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNANature, 450
Jikui Song, M. Teplova, Satoko Ishibe-Murakami, D. Patel (2012)
Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA MethylationScience, 335
K. Takeshita, I. Suetake, E. Yamashita, M. Suga, H. Narita, A. Nakagawa, S. Tajima (2011)
Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1)Proceedings of the National Academy of Sciences, 108
L. Davis, W. Kuehl, J. Battey (1986)
Basic methods in molecular biology
The N‐terminal regulatory part of DNA methyltransferase 1 (Dnmt1) contains a replication foci targeting sequence (RFTS) domain, which is involved in the recruitment of Dnmt1 to replication forks. The RFTS domain has been observed in a crystal structure to bind to the catalytic domain of the enzyme and block its catalytic centre. Removal of the RFTS domain led to activation of Dnmt1, thus suggesting an autoinhibitory role of this domain. Here, we destabilised the interaction of the RFTS domain with the catalytic domain by site‐directed mutagenesis and purified the corresponding Dnmt1 variants. Our data show that these mutations resulted in an up to fourfold increase in Dnmt1 methylation activity in vitro. Activation of Dnmt1 was not accompanied by a change in its preference for methylation of hemimethylated CpG sites. We also show that the Dnmt1 E572R/D575R variant has a higher DNA methylation activity in human cells after transfection into HCT116 cells, which are hypomorphic for Dnmt1. Our findings strongly support the autoinhibitory role of the RFTS domain, and indicate that it contributes to the regulation of Dnmt1 activity in cells.
ChemBioChem – Wiley
Published: Sep 21, 2015
Keywords: ; ; ;
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