Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1

Isamu Kameshita, Mari Sekiguchi, Daisuke Hamasaki, Yasunori Sugiyama, Naoya Hatano, Isao Suetake, Shoji Tajima, Noriyuki Sueyoshi

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1162-1167
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - Dec 26 2008
Externally publishedYes


  • Cyclin-dependent kinase-like 5
  • DNA methylation
  • DNA methyltransferase
  • DNA-binding protein
  • MeCP2
  • Protein kinase
  • Protein phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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