Comment | Published:

Relating DNA base-pairing in aqueous media to DNA polymerase fidelity

Nature Reviews Chemistry volume 1, Article number: 0074 (2017) | Download Citation

Controversy surrounds the perceived absence of a relationship between DNA polymerase fidelity (kinetic discrimination) and free energy changes determined from DNA melting studies (thermodynamic discrimination). Thermodynamic discrimination together with aqueous solvent effects can account for kinetic fidelities on the order of those observed experimentally.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    & Fidelity mechanisms in DNA replication. Annu. Rev. Biochem. 60, 477–511 (1991).

  2. 2.

    & The thermodynamics of DNA structural motifs. Annu. Rev. Biophys. Biomol. Struct. 33, 415–440 (2004).

  3. 3.

    et al. Kinetic selection versus free energy of DNA base pairing in control of polymerase fidelity. Proc. Natl Acad. Sci. USA 113, E2277–E2285 (2016).

  4. 4.

    & Enthalpy–entropy compensation in DNA melting thermodynamics. J. Biol. Chem. 270, 746–750 (1995).

  5. 5.

    , , & The energetic difference between synthesis of correct and incorrect base pairs accounts for highly accurate DNA replication. J. Am. Chem. Soc. 135, 1205–1208 (2013).

  6. 6.

    & Locations of frequently opening regions on natural DNAs and their relation to functional loci. Biopolymers 20, 1043–1058 (1981).

  7. 7.

    & Physical rationale behind the nonlinear enthalpy–entropy compensation in DNA duplex stability. J. Phys. Chem. B 113, 4698–4707 (2009).

  8. 8.

    & DNA polymerase fidelity: kinetics, structure, and checkpoints. Biochemistry 43, 14317–14324 (2004).

  9. 9.

    , & How DNA polymerases catalyse replication and repair with contrasting fidelity. Nat. Rev. Chem. 1, 0068 (2017).

  10. 10.

    et al. Mechanism of somatic hypermutation at the WA motif by human DNA polymerase η. Proc. Natl Acad. Sci. USA 110, 8146–8151 (2013).

Download references


The authors thank C. H. Mak and K. Oertell for insightful discussions, and J. G. Bertram for collating the data. This work was supported by the US National Institutes of Health (Grant Nos ES012259, U19CA177547 and GM214422 to M.F.G.).

Author information


  1. Department of Biological Sciences, University of Southern California.

    • John Petruska
    •  & Myron F. Goodman
  2. Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA.

    • Myron F. Goodman


  1. Search for John Petruska in:

  2. Search for Myron F. Goodman in:

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Myron F. Goodman.

About this article

Publication history



Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing