Studies on the Role of dam Methylation at the Escherichia Coli Chromosome Replication Origin (oriC)
The 245 bp replication origin of Escherichia coli. (oriC) contains 11 GATC whereas only one is expected at random (1). 8 of these GATC are conserved in the ori consensus sequence of the Enterobacteriacae (2). The regions around oriC are also GATC rich. This observation raises the question, why so much GATC in and around oriC ? A current view relates this phenomenon to the systematic adenine methylation of the GATC in Escherichia coli (dam methylation) (3). One hypothesis is that dam methylation is required for the functionning of oriC. For instance, dam methylation could help melting of DNA at oriC since A(CH3)-T base pairs are less stable than A-T ones (4). Indeed dam methylation lowers the calculated DNA duplex stability profile of oriC (4). In contradiction with the above hypothesis, a dam - mutant without residual methylation at oriC grows well (5). Nevertheless, since a dam - polA - double mutant is lethal (6), one can imagine that new DNA initiation mechanism dependent on DNA polymerase I occurs in dam - mutants. A second hypothesis to explain the abundance of GATC in and around oriC is that GATC tend to concentrate mismatch repair enzymes in that region, enhancing conservation of their DNA sequence (1).
KeywordsMismatch Repair Plasmid Replication GATC Site GATC Sequence Residual Methylation
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