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Specialized DNA polymerases, cellular survival, and the genesis of mutations

Errol C Friedberg1, Robert Wagner, Miroslav Radman

  • 1Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. errol.friedberg@utsouthwestern.edu

Science (New York, N.Y.)
|June 1, 2002
PubMed

Insights

Specialized DNA polymerases bypass DNA damage, preventing cell death. While accurate on damaged DNA, their low fidelity on undamaged DNA may serve functions like generating immune diversity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Cell death can occur due to replication arrest when DNA is damaged or altered.
  • Multiple DNA polymerases exist in cells to specifically bypass DNA damage.
  • Translesion DNA synthesis (TLS) polymerases are crucial for replicating damaged DNA.

Purpose of the Study:

  • To investigate the fidelity of specialized DNA polymerases during translesion DNA synthesis.
  • To understand the implications of DNA polymerase fidelity on both damaged and undamaged DNA.
  • To explore the potential physiological roles of low-fidelity DNA synthesis.

Main Methods:

  • Analysis of DNA polymerase activity and fidelity.
  • In vitro assays for translesion DNA synthesis.
  • Examination of DNA polymerase substrate specificity.

Main Results:

  • Specialized DNA polymerases effectively bypass specific DNA lesions with high fidelity.
  • These polymerases exhibit significantly reduced fidelity on undamaged DNA.
  • Low fidelity on undamaged DNA was observed even with non-cognate lesions.

Conclusions:

  • Specialized DNA polymerases are essential for preventing cell death from DNA damage.
  • The reduced fidelity of some polymerases on undamaged DNA is a key characteristic.
  • This low fidelity may be a functional mechanism, for example, in generating immunoglobulin diversity.

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