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

Berkyurek, Ahmet Can; Suetake, Isao; Arita, Kyohei; Takeshita, Kohei; Nakagawa, Atushi; Shirakawa, Masahiro; Tajima, Shoji

doi:https://doi.org/10.1074/jbc.M113.523209

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

Berkyurek, Ahmet Can; Suetake, Isao; Arita, Kyohei et al.

Journal of Biological Chemistry, 2014, 289(1), 379-386

Number of Access:861（2025-09-29 10:03 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73664

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Title	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
Creator	CreatorName Berkyurek, Ahmet Can
	NRID 1000080304054 1000080304054 CreatorName Suetake, Isao
	NRID 1000040549648 1000040549648 CreatorName Arita, Kyohei
	NRID 1000080346808 1000080346808 CreatorName Takeshita, Kohei
	NRID 1000020188890 1000020188890 ORCID 0000-0002-1700-7861 0000-0002-1700-7861 researchmap permalink atsushi_nakagawa atsushi_nakagawa Scopus Author ID 7202934909 7202934909 CreatorName Nakagawa, Atushi
	NRID 1000000202119 1000000202119 CreatorName Shirakawa, Masahiro
	NRID 1000050132931 1000050132931 CreatorName Tajima, Shoji
Description	This research was originally published in Journal of Biological Chemistry. Ahmet Can Berkyurek, Isao Suetake, Kyohei Arita, Kohei Takeshita, Atsushi Nakagawa, Masahiro Shirakawa and Shoji Tajima. 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. Journal of Biological Chemistry. 2014; 289, 379-386. © the American Society for Biochemistry and Molecular Biology.
Abstract	Dnmt1 is responsible for the maintenance DNA methylation during replication to propagate methylation patterns to the next generation. The replication foci targeting sequence (RFTS), which plugs the catalytic pocket, is necessary for recruitment of Dnmt1 to the replication site. In the present study we found that the DNA methylation activity of Dnmt1 was DNA length-dependent and scarcely methylated 12-bp short hemi-methylated DNA. Contrarily, the RFTS-deleted Dnmt1 and Dnmt1 mutants that destroyed the hydrogen bonds between the RFTS and catalytic domain showed significant DNA methylation activity even toward 12-bp hemi-methylated DNA. The DNA methylation activity of the RFTS-deleted Dnmt1 toward 12-bp hemi-methylated DNA was strongly inhibited on the addition of RFTS, but to a lesser extent by Dnmt1 harboring the mutations that impair the hydrogen bond formation. The SRA domain of Uhrf1, which is a prerequisite factor for maintenance methylation and selectively binds to hemi-methylated DNA, stimulated the DNA methylation activity of Dnmt1. The SRA to Dnmt1 concentration ratio was the determinant for the maximum stimulation. In addition, a mutant SRA, which had lost the DNA binding activity but was able to bind to Dnmt1, stimulated the DNA methylation activity of Dnmt1. The results indicate that the DNA methylation activity of Dnmt1 was stimulated on the direct interaction of the SRA and Dnmt1. The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	289(1)
Page	379-386
Date of Issued	2014-01
Language	English
Handle URL	https://hdl.handle.net/11094/73664
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M113.523209
Relation.isIdenticalTo	PMID 24253042
Access Rights	open access
CopyRight	© the American Society for Biochemistry and Molecular Biology.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2014, 289(1), p. 379-386
DC.title	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
DC.creator	Berkyurek, Ahmet Can
	Suetake, Isao
	Arita, Kyohei
	Takeshita, Kohei
	Nakagawa, Atushi
	Shirakawa, Masahiro
	Tajima, Shoji
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2014-01
DC.identifier	https://doi.org/10.1074/jbc.M113.523209
DC.description	This research was originally published in Journal of Biological Chemistry. Ahmet Can Berkyurek, Isao Suetake, Kyohei Arita, Kohei Takeshita, Atsushi Nakagawa, Masahiro Shirakawa and Shoji Tajima. 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. Journal of Biological Chemistry. 2014; 289, 379-386. © the American Society for Biochemistry and Molecular Biology.
DCTERMS.abstract	Dnmt1 is responsible for the maintenance DNA methylation during replication to propagate methylation patterns to the next generation. The replication foci targeting sequence (RFTS), which plugs the catalytic pocket, is necessary for recruitment of Dnmt1 to the replication site. In the present study we found that the DNA methylation activity of Dnmt1 was DNA length-dependent and scarcely methylated 12-bp short hemi-methylated DNA. Contrarily, the RFTS-deleted Dnmt1 and Dnmt1 mutants that destroyed the hydrogen bonds between the RFTS and catalytic domain showed significant DNA methylation activity even toward 12-bp hemi-methylated DNA. The DNA methylation activity of the RFTS-deleted Dnmt1 toward 12-bp hemi-methylated DNA was strongly inhibited on the addition of RFTS, but to a lesser extent by Dnmt1 harboring the mutations that impair the hydrogen bond formation. The SRA domain of Uhrf1, which is a prerequisite factor for maintenance methylation and selectively binds to hemi-methylated DNA, stimulated the DNA methylation activity of Dnmt1. The SRA to Dnmt1 concentration ratio was the determinant for the maximum stimulation. In addition, a mutant SRA, which had lost the DNA binding activity but was able to bind to Dnmt1, stimulated the DNA methylation activity of Dnmt1. The results indicate that the DNA methylation activity of Dnmt1 was stimulated on the direct interaction of the SRA and Dnmt1. The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center.
DC.rights	© the American Society for Biochemistry and Molecular Biology.
DC.format	73664
citation_title	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
citation_author	Berkyurek, Ahmet Can
	Suetake, Isao
	Arita, Kyohei
	Takeshita, Kohei
	Nakagawa, Atushi
	Shirakawa, Masahiro
	Tajima, Shoji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2014-01
citation_journal_title	Journal of Biological Chemistry
citation_volume	289
citation_issue	1
citation_firstpage	379
citation_lastpage	386
citation_doi	https://doi.org/10.1074/jbc.M113.523209
citation_pmid	24253042
citation_public_url	https://hdl.handle.net/11094/73664

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

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