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Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
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Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair

Published on: May 24, 2017

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Recognition and removal of clustered DNA lesions via nucleotide excision repair

N V Naumenko1, I O Petruseva1, A A Lomzov1

  • 1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.

DNA Repair
|September 25, 2021
PubMed

Insights

The presence of clustered DNA damage, specifically a diethylene glycol phosphodiester (DEG) analog, hinders the repair of bulky lesions. The XPC-RAD23B protein shows increased affinity for this clustered damage, impacting DNA repair efficiency.

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Biochemistry

Background:

  • Clustered DNA damage involves multiple lesions within a short DNA segment.
  • Such damage can arise from potent genotoxic agents, especially in cells with impaired repair pathways.
  • Understanding the repair of complex DNA lesions is crucial for cellular health.

Purpose of the Study:

  • To investigate the impact of a diethylene glycol phosphodiester (DEG) analog on the repair of a bulky DNA lesion (nFlu) by mammalian nucleotide excision repair.
  • To determine how the proximity of DEG to nFlu affects the recognition and removal of the bulky lesion.
  • To assess the role of the XPC-RAD23B protein complex in recognizing clustered DNA damage.

Main Methods:

  • In vitro analysis of DNA repair by mammalian nucleotide excision repair system.
  • Biochemical assays to measure protein-DNA binding affinity.
  • Molecular dynamics simulations to study DNA structural changes.

Main Results:

  • The removal efficiency of the bulky nFlu lesion was reduced by the presence of DEG in the complementary DNA strand.
  • Complete suppression of nFlu removal occurred when DEG was positioned opposite the nFlu lesion.
  • The XPC-RAD23B complex exhibited a higher affinity for DNA with clustered damage compared to single lesions, with affinity increasing as lesions drew closer.
  • Alterations in DNA double-helix geometry due to clustered damage were identified.

Conclusions:

  • The proximity and type of lesions within clustered DNA damage significantly influence the efficiency of nucleotide excision repair.
  • The XPC-RAD23B complex plays a key role in recognizing and potentially initiating the repair of clustered DNA lesions.
  • Structural changes in DNA associated with clustered damage are critical determinants of repair outcomes.
Keywords:
Clustered DNA lesionsHigher eukaryoteMolecular dynamicsMultiple DNA lesionsNucleotide excision repair

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