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Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities

Maroof K Zafar1, Robert L Eoff1

  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205-7199, United States.

Chemical Research in Toxicology
|August 26, 2017
PubMed

Insights

Cancer cells use DNA damage tolerance (DDT) pathways, including translesion DNA synthesis (TLS), to survive replication stress. Inhibiting TLS could enhance cancer therapies by targeting these survival mechanisms.

Area of Science:

  • Genomic instability in cancer
  • DNA damage tolerance (DDT) mechanisms
  • Translesion DNA synthesis (TLS) pathways

Background:

  • Cancer is characterized by genomic instability, driven by complex mechanisms.
  • Cellular responses to DNA damage and replication stress impact tumor stability and therapeutic response.
  • DNA damage tolerance (DDT) is crucial for maintaining genomic integrity and contributes to cancer development.

Purpose of the Study:

  • To summarize DDT mechanisms and the misregulation of TLS in cancer.
  • To explore the potential of targeting TLS pathways for improved cancer therapies.

Main Methods:

  • Review of existing literature on DDT and TLS.
  • Analysis of the role of TLS in DNA adduct bypass and replication stress resolution.
  • Discussion of TLS involvement in tumor heterogeneity and cancer stem cell maintenance.

Main Results:

  • TLS facilitates the bypass of DNA lesions, including those induced by genotoxic drugs.
  • Misregulation of TLS contributes to cancer etiology and progression.
  • TLS pathways are implicated in maintaining the cancer stem cell niche.

Conclusions:

  • Targeting TLS represents a promising strategy to enhance the efficacy of current cancer treatments.
  • Understanding TLS mechanisms is key to developing novel therapeutic approaches for cancer.

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