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Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Updated: May 3, 2026

Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Damage-induced i-loops generate eccDNA from repetitive elements.

Elia Zanella1, Michele Giannattasio2, Sara Bisi3

  • 1IFOM ETS - The AIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milano, Italy.

Molecular Cell
|May 1, 2026
PubMed
Summary
This summary is machine-generated.

A novel mechanism for extrachromosomal circular DNA (eccDNA) formation involves internal loops (i-loops) arising from single-stranded DNA breaks, distinct from DNA end joining. This process, triggered by apoptosis, sheds light on eccDNA

Keywords:
DNA damagealpha satelliteapoptosiscancercentromeresecDNAeccDNAnon-allelic homologous recombinationrDNArepetitive DNAretrotransposonssingle-stranded breakstelomeres

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Extrachromosomal circular DNA (eccDNA) is implicated in genome instability and tumorigenesis.
  • Existing models of eccDNA formation primarily focus on double-stranded breaks (DSBs) and DNA end joining.
  • A comprehensive understanding of eccDNA biogenesis is crucial for addressing its role in disease and evolution.

Purpose of the Study:

  • To elucidate a novel mechanism of eccDNA formation in human cells.
  • To investigate the role of single-stranded DNA (ssDNA) breaks and internal loops (i-loops) in eccDNA biogenesis.
  • To explore the contribution of this mechanism to eccDNA formation during apoptosis and its implications for cancer biology.

Main Methods:

  • Utilized electron microscopy (EM) to visualize i-loops as precursors to eccDNA.
  • Employed rolling-circle amplification to detect eccDNA formation.
  • Applied Nanopore sequencing to identify repetitive elements involved in eccDNA generation during apoptosis.

Main Results:

  • Identified a new pathway for eccDNA formation initiated by ssDNA breaks or gaps, leading to the formation of internal loops (i-loops) at repetitive sequences like telomeres and alpha satellites.
  • Demonstrated that i-loops are direct precursors to eccDNA, which can be visualized by EM and detected by rolling-circle amplification.
  • Showed that apoptosis significantly triggers i-loop and eccDNA formation at telomeric and alpha satellite repeats, with Nanopore sequencing revealing other repetitive elements like rDNA and retrotransposons as additional sources during this process.

Conclusions:

  • Proposed a novel i-loop-mediated mechanism for eccDNA formation, distinct from DNA end joining, driven by ssDNA breaks or gaps.
  • Highlighted apoptosis as a key cellular event that activates this i-loop mechanism, leading to eccDNA generation.
  • Suggested that the i-loop mechanism significantly contributes to the pool of eccDNA in human cells, with broad implications for genome instability, tumor biology, and genome evolution.