Accuracy of DNA synthesis and apparent accuracy of DNA methylation

Range DNA synthesis 1 ‘unforced’ error for every 10^7–10^8 bases copied: DNA methylation ~96%
Organism Various
Reference Bird A. Perceptions of epigenetics. Nature. 2007 May 24 447(7143):396-8. DOI: 10.1038/nature05913 p.398 left column top paragraphPubMed ID17522671
Primary Source [13] Kunkel TA. DNA replication fidelity. J Biol Chem. 2004 Apr 23 279(17):16895-8. DOI: 10.1074/jbc.R400006200 [14] Laird CD, Hairpin-bisulfite PCR: assessing epigenetic methylation patterns on complementary strands of individual DNA molecules. Proc Natl Acad Sci U S A. 2004 Jan 6 101(1):204-9. DOI: 10.1073/pnas.2536758100PubMed ID14988392, 14673087
Method Primary source [14] abstract: "A central unresolved question in epigenetics concerns the mechanisms by which a locus maintains, or changes, its state of cytosine methylation. [Investigators] developed "hairpin-bisulfite PCR" to analyze these mechanisms. This method reveals the extent of methylation symmetry between the complementary strands of individual DNA molecules. Using hairpin-bisulfite PCR, [they] determined the fidelity of methylation transmission in the CpG island of the FMR1 gene in human lymphocytes. For the hypermethylated CpG island of this gene, characteristic of inactive-X alleles, [they] estimate a maintenance methylation efficiency of approximately 0.96 per site per cell division."
Comments P.397 right column bottom paragraph: "The issue of replicative accuracy is also relevant when considering heritability. DNA synthesis is spectacularly accurate, making only 1 'unforced' error for every 10^7–10^8 bases copied [primary source 13]. But DNA methylation has an apparent accuracy of ~96%, which is ~1 error for every 25 methylated sites copied [primary source 14]. Because of this error rate, cloning from a single cell quickly results in a population of cells in which DNA methylation patterns are diverse [ref 15]." Primary source [13] gives value for E. coli & phage (p.16895 left column 2nd paragraph therein: "Studies of bacteriophage and Escherichia coli replication in the absence of DNA mismatch repair and external environmental stress suggest that the base substitution error rate of the replication machinery in vivo is in the range of 10^-7 to 10^-8 (ref 4 therein)". Primary source [14] studied human lymphocytes
Entered by Uri M
ID 112981