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Updated: Sep 28, 2026

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
How DNA lesions are turned into mutations within cells?
Vincent Pagès1, Robert P P Fuchs
1UPR 9003 du CNRS, Cancerogenese et Mutagenese Moleculaire et Structurale, UPR Conventionnee avec l'Universite Louis Pasteur, ESBS, Blvd S. Brant, 67400 Strasbourg, France.
Abstract:
Genomes of all living organisms are constantly injured by endogenous and exogenous agents that modify the chemical integrity of DNA and in turn challenge its informational content. Despite the efficient action of numerous repair systems that remove lesions in DNA in an error-free manner, some lesions, that escape these repair mechanisms, are present when DNA is being replicated. Although replicative DNA polymerases are usually unable to copy past such lesions, it was recently discovered that cells are equipped with specialized DNA polymerases that will assist the replicative polymerase during the process of Translesion Synthesis (TLS). These TLS polymerases exhibit relaxed fidelity that allows them to copy past lesions in DNA with an inherent risk of generating mutations at high frequency. We present recent aspects related to the genetics and biochemistry of TLS and highlight some of the remaining hot topics of this field.
Insights
DNA damage is repaired by specialized enzymes, but some lesions persist. Translesion Synthesis (TLS) polymerases copy past DNA damage, albeit with a risk of mutations, which is a key area of ongoing research.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Genomes face constant damage from internal and external sources, affecting DNA integrity.
- While DNA repair systems are efficient, some lesions escape removal before replication.
- Replicative DNA polymerases struggle to bypass DNA lesions, necessitating alternative mechanisms.
Purpose of the Study:
- To review recent advancements in the genetics and biochemistry of Translesion Synthesis (TLS).
- To identify and discuss current challenges and hot topics in TLS research.
Main Methods:
- Review of current literature on Translesion Synthesis.
- Analysis of genetic and biochemical data related to TLS polymerases.
Main Results:
- Discovery of specialized DNA polymerases that facilitate Translesion Synthesis (TLS).
- TLS polymerases possess relaxed fidelity, enabling bypass of DNA lesions.
- TLS activity carries a significant risk of inducing mutations due to low fidelity.
Conclusions:
- Translesion Synthesis is a critical cellular mechanism for replicating damaged DNA.
- The relaxed fidelity of TLS polymerases is essential for survival but introduces mutagenic potential.
- Further research is needed to fully understand the genetics, biochemistry, and implications of TLS.
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