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Author Spotlight: Advanced Single-Molecule Techniques for Investigating Telomeric Protein-DNA Interactions
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Interstitial telomeric repeats-associated DNA breaks.

Olga Shubernetskaya1, Dmitry Skvortsov1, Sergey Evfratov1

  • 1a Chemistry Department , M.V. Lomonosov Moscow State University , Moscow , Russia.

Nucleus (Austin, Tex.)
|September 16, 2017
PubMed
Summary

Persistent DNA breaks occur at interstitial telomeric repeats in zebrafish and mouse embryos. These breaks form discrete foci, are not linked to apoptosis or replication, and show tissue-specific patterns.

Keywords:
ChromatinDNA breaksETUNELdevelopmentinterstitial telomeric repeatsmousezebrafish

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Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • DNA breaks are common during a cell's life but usually repaired.
  • Telomeres protect chromosome ends, but shorter telomeric repeats exist within eukaryotic genomes.
  • The function and persistence of DNA breaks at interstitial telomeric repeats are not well understood.

Purpose of the Study:

  • To investigate the potential association between interstitial telomeric repeats and persistent DNA breaks.
  • To characterize the nature and distribution of these breaks in developing organisms.

Main Methods:

  • Observation of DNA breakage foci in zebrafish and mouse embryos.
  • Analysis of breaks independent of apoptosis and replication.
  • Development of a PCR-based method to amplify DNA between inverted telomeric repeats.
  • Cloning and sequencing of amplified DNA fragments.

Main Results:

  • Numerous discrete DNA breakage foci were identified in zebrafish and mouse embryos.
  • These breaks were not associated with cell death or replication and did not activate DNA damage response.
  • A PCR method successfully amplified DNA regions between inverted telomeric repeats linked to breaks.
  • Sequencing revealed tissue-specific and developmental stage-specific patterns in the distribution of these DNA fragments.

Conclusions:

  • Interstitial telomeric repeats can be sites of persistent DNA breaks in eukaryotic genomes.
  • These breaks form distinct foci and their occurrence is regulated in a tissue- and stage-specific manner.
  • The findings suggest a novel role for interstitial telomeric repeats in genome stability and regulation during development.