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Mechanisms of mutagenesis: DNA replication in the presence of DNA damage

Binyan Liu1, Qizhen Xue1, Yong Tang1

  • 1Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.

Mutation Research. Reviews in Mutation Research
|May 29, 2016
PubMed

Insights

Environmental mutagens cause DNA damage, leading to mutations and diseases like cancer. This review explores how DNA damage affects replication fidelity and mutagenesis in both single DNA polymerases and complex DNA replisomes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Environmental mutagens induce DNA damage, which can lead to mutations and diseases such as cancer.
  • DNA replication is a critical process susceptible to damage, impacting cellular health.
  • Understanding mutagenesis mechanisms is crucial for disease prevention and treatment.

Purpose of the Study:

  • To review the molecular mechanisms of mutagenesis arising from DNA damage during DNA replication.
  • To compare mutagenesis mechanisms at the single DNA polymerase level and the complex DNA replisome level.
  • To discuss the role of translesion DNA synthesis in bypassing DNA damage.

Main Methods:

  • Review of existing literature on DNA replication and mutagenesis.
  • Analysis of mechanisms in various model organisms (bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast, human).
  • Inclusion of recent findings using new methods to investigate DNA damage bypass in replisomes.

Main Results:

  • DNA damage affects single DNA polymerase replication by reducing fidelity, causing frameshift mutations, or blocking replication.
  • The DNA replisome's protein interactions and accessory proteins can lead to varied mutagenesis outcomes.
  • New techniques allow investigation into how replisomes from different organisms and human cell extracts handle DNA damage bypass.

Conclusions:

  • Mutagenesis mechanisms differ significantly between single DNA polymerases and complex DNA replisomes.
  • Investigating DNA damage replication and bypass is essential for understanding cancer and other diseases.
  • Translesion DNA synthesis plays a key role in navigating DNA damage during replication.
Keywords:
DNA damageDNA replicationEnvironmental mutagensMutationPolymeraseReplisome

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