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DNA lesions piece together impossible trees

Claudia Arnedo-Pac1, Sarah J Aitken2

  • 1Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK.

Trends in Genetics : TIG
|April 3, 2025
PubMed

Insights

DNA lesions can persist for years, leading to mutations and somatic mosaicism. This study reveals their long-lasting impact, even from exposures during development.

Area of Science:

  • Genetics
  • Molecular Biology
  • Genomics

Background:

  • DNA damage is a critical factor in genome instability.
  • Persistent DNA lesions can lead to mutations, strand asymmetry, and somatic mosaicism.
  • Understanding the persistence of DNA lesions is crucial for comprehending long-term health effects.

Purpose of the Study:

  • To investigate the duration of DNA lesion persistence within cells.
  • To determine the long-term consequences of endogenous DNA damage.
  • To explore the origins of persistent DNA lesions, including in utero exposures.

Main Methods:

  • Analysis of DNA lesion persistence across multiple cell cycles.
  • Investigating mutational strand asymmetry and multiallelic variation.
  • Tracking the fate of DNA lesions from endogenous exposures.

Main Results:

  • DNA lesions can persist for extended periods, lasting months to years.
  • Persistent lesions contribute to significant genetic alterations, including somatic mosaicism.
  • Endogenous exposures, even in utero, can initiate long-lasting DNA damage.

Conclusions:

  • DNA lesions possess remarkable persistence, impacting genomic integrity over long timescales.
  • The long lifespan of DNA lesions underscores their potential role in chronic diseases and aging.
  • Further research is warranted to fully elucidate the mechanisms and implications of persistent DNA damage.
Keywords:
DNA damageDNA lesionlesion segregationmultiallelismmutagenesisphylogenetics

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