Postreplicative maintenance of genomic methylation patterns was proposed to 
depend largely on the binding of DNA methyltransferase 1 (Dnmt1) to PCNA, a core 
component of the replication machinery. We investigated how the slow and 
discontinuous DNA methylation could be mechanistically linked with fast and 
processive DNA replication. Using photobleaching and quantitative live cell 
imaging we show that Dnmt1 binding to PCNA is highly dynamic. Activity 
measurements of a PCNA-binding-deficient mutant with an enzyme-trapping assay in 
living cells showed that this interaction accounts for a 2-fold increase in 
methylation efficiency. Expression of this mutant in mouse dnmt1-/- embryonic 
stem (ES) cells restored CpG island methylation. Thus association of Dnmt1 with 
the replication machinery enhances methylation efficiency, but is not strictly 
required for maintaining global methylation. The transient nature of this 
interaction accommodates the different kinetics of DNA replication and 
methylation while contributing to faithful propagation of epigenetic 
information.