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

アクセス数:286件（2025-04-25 19:38 集計）

固定URL: https://hdl.handle.net/11094/73664

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タイトル	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
著者	著者名 Berkyurek, Ahmet Can
	NRID 1000080304054 1000080304054 著者名 Suetake, Isao
	NRID 1000040549648 1000040549648 著者名 Arita, Kyohei
	NRID 1000080346808 1000080346808 著者名 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 著者名 Nakagawa, Atushi
	NRID 1000000202119 1000000202119 著者名 Shirakawa, Masahiro
	NRID 1000050132931 1000050132931 著者名 Tajima, Shoji
内容	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.
抄録	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.
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	289(1)
ページ	379-386
刊行年月	2014-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/73664
eISSN	1083351X
NCID	AA1202441X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1074/jbc.M113.523209
関連情報 (isIdenticalTo)	PMID 24253042
アクセス権	open access
権利情報	© the American Society for Biochemistry and Molecular Biology.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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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