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Translesion synthesis by RNA polymerases: occurrence and biological implications for transcriptional mutagenesis

Paul W Doetsch1

  • 1Department of Biochemistry and Division of Cancer Biology, Emory University School of Medicine, 4013 Rollins Research Center, Atlanta, GA 30322, USA. medpwd@emory.edu

Mutation Research
|December 3, 2002
PubMed

Insights

DNA damage can cause mutations. This review explores transcriptional mutagenesis, where RNA polymerase bypasses DNA lesions, leading to altered proteins, especially in non-dividing cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Organisms' genes face constant damage from physical and chemical agents.
  • Unrepaired DNA damage can lead to harmful consequences, including altered cellular phenotypes due to mutant proteins.
  • Most studies focus on DNA polymerase errors, overlooking other mutagenesis mechanisms.

Purpose of the Study:

  • To review recent research on transcriptional mutagenesis.
  • To highlight the role of RNA polymerase in bypassing DNA lesions.
  • To discuss the implications of mutations arising during transcription.

Main Methods:

  • Review of existing literature on translesion synthesis by RNA polymerases.
  • Analysis of studies investigating transcriptional mutagenesis.
  • Discussion of experimental findings on DNA damage bypass by transcriptional machinery.

Main Results:

  • Over a dozen DNA damage types are bypassed by the transcriptional machinery.
  • RNA polymerase exhibits varying efficiencies and miscoding potentials when bypassing lesions.
  • Transcriptional mutagenesis produces mutant transcripts and subsequently mutant proteins.

Conclusions:

  • Transcriptional mutagenesis is a significant source of mutant proteins, particularly in non-dividing cells.
  • RNA polymerase plays a crucial role in generating mutations by bypassing DNA damage.
  • Understanding transcriptional mutagenesis is vital for comprehending cellular responses to DNA damage and its biological implications.

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