Specialized DNA Polymerases, Cellular Survival, and the Genesis of Mutations

Science 31 May 2002:
Vol. 296 no. 5573 pp. 1627-1630
DOI: 10.1126/science.1070236
  • Review

Specialized DNA Polymerases, Cellular Survival, and the Genesis of Mutations

  1. Errol C. Friedberg1,*,
  2. Robert Wagner2,
  3. Miroslav Radman3

+ Author Affiliations

  1. 1 Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  2. 2 Gene Check Inc., 1629 Blue Spruce Drive, Fort Collins, CO 80524, USA.
  3. 3 Evolutionary and Medical Molecular Genetics, INSERM E9916, Medical Faculty Necker–Enfants Malades, University of Paris-V, 156 Rue de Vaugirard, 75730 Paris Cedex 15, France.

Abstract

Cell death caused by arrested replication of damaged or structurally altered DNA can be avoided in prokaryotic and eukaryotic cells by multiple DNA polymerases that are specialized to bypass DNA damage. Some of these polymerases perform such translesion DNA synthesis of specific types of damage with high genetic fidelity. However, they exhibit greatly reduced fidelity when they operate on undamaged DNA or on DNA with lesions that are (apparently) not cognate substrates. The low fidelity of some of these specialized polymerases when copying undamaged DNA may be physiologically functional, including generating immunoglobulin diversity.

 

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