title: Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1.
abstract: DNA methyltransferase 1 (Dnmt1) is an enzyme that recognizes and methylates hemimethylated CpG after DNA replication to maintain methylation patterns. Although the N-terminal region of Dnmt1 is known to interact with various proteins, such as methyl-CpG-binding protein 2 (MeCP2), the associations of protein kinases with this region have not been reported. In the present study, we found that a 110-kDa protein kinase in mouse brain could bind to the N-terminal domain of Dnmt1. This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found to colocalize in nuclei and appeared to interact with each other. Catalytically active CDKL5, CDKL5(1-352), phosphorylated the N-terminal region of Dnmt1 in the presence of DNA. Considering that defects in the MeCP2 or CDKL5 genes cause Rett syndrome, we propose that the interaction between Dnmt1 and CDKL5 may contribute to the pathogenic processes of Rett syndrome.
authors.affiliation: Department of Life Sciences, Faculty of Agriculture, Kagawa University, Ikenobe 2393, Miki-cho, Kagawa 761-0795, Japan. kamesita@ag.kagawa-u.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Kameshita
authors.forename: Mari
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamasaki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Naoya
authors.initials: N
authors.lastname: Hatano
authors.forename: Isao
authors.initials: I
authors.lastname: Suetake
authors.forename: Shoji
authors.initials: S
authors.lastname: Tajima
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sueyoshi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015518:Rett Syndrome / Q000201:enzymology; D017384:Sequence Deletion
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C533690:CDKL5 protein, mouse