DNA Replication Fidelity

Abstract

DNA polymerases are proteins that catalyse the polymerization of DNA. Fidelity in this process refers to the ability of the polymerase to avoid or to correct errors in the newly synthesized DNA strand.

Keywords: DNA polymerase; DNA replication; replicational fidelity; Y family polymerases; xeroderma pigmentosum; mutation

Figure 1.

Steps of deoxyribonucleic acid (DNA) polymerization depicting the correct incorporation of thymidine 5′‐monophosphate. The ‘thumb’, ‘palm’ and ‘finger’ domains are shown in purple, blue and orange respectively. The green domain represents the ‘PAD’ or ‘little finger’ domain that has thus far been identified only in low‐fidelity Y family DNA polymerases. The red transluscent domain (in two of the drawings) represents the 3′→5′ exonuclease domain, which is not present in Y family polymerases. ‘†’ represents the transition state for enzyme catalysis. dTTP: thymidine 5′‐triphosphate; PPi: pyrophosphate; dTMP: thymidine 5′‐monophosphate. The curved black arrows denote movement of the ‘thumb’ and ‘fingers’ domains.

close

References

Beckman RA and Loeb LA (1993) Multi‐stage proofreading in DNA replication. Quarterly Reviews in Biophysics 26: 225–331.

Benkovic SJ and Cameron CE (1995) Kinetic analysis of nucleotide incorporation and misincorporation by Klenow fragment of Escherichia coli DNA polymerase I. Methods in Enzymology 262: 257–269.

Friedberg EC, Fischhaber PL and Kisker C (2001) Error‐prone DNA polymerases: novel structures and the benefits of infidelity. Cell 107: 9–12.

Friedberg EC, Wagner R and Radman M (2002) Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science 296: 1627–1630.

Gearhart PJ and Wood RD (2001) Emerging links between hypermutation of antibody genes and DNA polymerases. Nature Reviews in Immunology 1: 187–192.

Loeb LA (1991) Mutator phenotype may be required for multistage carcinogenesis. Cancer Research 51: 3075–3079.

Ohmori H, Friedberg EC, Fuchs RP, et al. (2001) The Y‐family of DNA polymerases. Molecular Cell 8: 7–8.

Patel PH and Loeb LA (2001) Getting a grip on how DNA polymerases function. Nature Structural Biology 8: 656–659.

Pavlov YI, Newlon CS and Kunkel TA (2002) Yeast origins establish a strand bias for replicational mutagenesis. Molecular Cell 10: 207–213.

Prakash S and Prakash L (2002) Translesion DNA synthesis in eukaryotes: a one‐ or two‐polymerase affair. Genes and Development 16: 1872–1883.

Further Reading

Franklin MC, Wang J and Steitz TA (2001) Structure of the replicating complex of a pol alpha family DNA polymerase. Cell 105: 657–667.

Fisher PA (1994) Enzymologic mechanism of replicative DNA polymerases in higher eukaryotes. Progress in Nucleic Acid Research in Molecular Biology 47: 371–397.

Goodman MF (1997) Hydrogen bonding revisited: geometric selection as a principal determinant of DNA replication fidelity. Proceedings of the National Academy of Sciences of the United States of America 94: 10493–10495.

Kool ET (1998) Replication of non‐hydrogen bonded bases by DNA polymerases: a mechanism for steric matching. Biopolymers 48: 3–17.

Kunkel TA and Bebenek K (2000) DNA replication fidelity. Annual Review of Biochemistry 69: 497–529.

Loeb LA (1998) Cancer cells exhibit a mutator phenotype. Advances in Cancer Research 72: 25–56.

Radman M (1998) DNA replication: one strand may be more equal. Proceedings of the National Academy of Sciences of the United States of America 95: 9718–9719.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Friedberg, Errol C, and Fischhaber, Paula L(Jan 2006) DNA Replication Fidelity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006172]