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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Transcription reprogramming and endogenous DNA damage.

Lei Li1

  • 1Life Sciences Institute, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, China.

DNA Repair
|September 4, 2024
PubMed
Summary

Cellular differentiation involves transcription reprogramming, which can cause DNA damage and threaten genome stability. This review explores DNA damage formation, removal mechanisms, and related diseases during transcription reprogramming.

Keywords:
Aldehyde dehydrogenaseDNA interstrand crosslinkDNA-protein crosslinkDemethylationDifferentiationEndogenous DNA damageEpigeneticsFormaldehydeR-loopTranscription reprogramming

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Transcription reprogramming is crucial for cell dynamics like differentiation and stress responses.
  • This process can lead to adverse effects that compromise genomic stability.
  • Endogenous DNA damage and lesions arise during transcription reprogramming.

Purpose of the Study:

  • To review the mechanisms of DNA damage formation during cellular differentiation.
  • To discuss cellular pathways involved in removing these DNA lesions.
  • To explore diseases associated with transcription reprogramming and genomic instability.

Main Methods:

  • Literature review of studies on transcription, DNA damage, and cellular repair mechanisms.
  • Analysis of endogenous DNA damage pathways including formaldehyde generation and R-loop accumulation.
  • Examination of DNA glycosylase activity in relation to DNA strand breaks.

Main Results:

  • Oxidative protein demethylation generates formaldehyde, causing DNA crosslinking.
  • High transcription levels can lead to unscheduled R-loop formation.
  • DNA glycosylase activity during imprint reversal can cause DNA strand breaks.

Conclusions:

  • Transcription reprogramming during cellular differentiation poses a significant threat to genome stability due to endogenous DNA damage.
  • Understanding these damage pathways and repair mechanisms is vital for comprehending associated diseases.
  • Further research is needed to elucidate the full spectrum of diseases linked to transcription reprogramming-induced genomic instability.