A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei

Cell. 1992 Nov 27;71(5):865-73. doi: 10.1016/0092-8674(92)90561-p.


Tissue-specific patterns of methylated deoxycytidine residues in the mammalian genome are preserved by postreplicative methylation of newly synthesized DNA. DNA methyltransferase (MTase) is here shown to associate with replication foci during S phase but to display a diffuse nucleoplasmic distribution in non-S phase cells. Analysis of DNA MTase-beta-galactosidase fusion proteins has shown that association with replication foci is mediated by a novel targeting sequence located near the N-terminus of DNA MTase. This sequence has the properties expected of a targeting sequence in that it is not required for enzymatic activity, prevents proper targeting when deleted, and, when fused to beta-galactosidase, causes the fusion protein to associate with replication foci in a cell cycle-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Compartmentation
  • Cell Cycle
  • Cell Nucleus / enzymology
  • Cell Nucleus / ultrastructure
  • DNA Replication*
  • DNA-Cytosine Methylases / metabolism*
  • In Vitro Techniques
  • Mice
  • Recombinant Fusion Proteins / metabolism
  • S Phase*
  • Sequence Deletion
  • Structure-Activity Relationship


  • Recombinant Fusion Proteins
  • DNA-Cytosine Methylases