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Updated: Aug 9, 2025

Author Spotlight: Visualizing Single-Stranded DNA During DNA Repair for Therapeutic Insights
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Single-strand mismatch and damage patterns revealed by single-molecule DNA sequencing.

Mei Hong Liu1,2, Benjamin Costa1,2, Una Choi1,2

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Scientists developed a novel sequencing method to detect initial single-strand DNA damage and mismatches. This breakthrough reveals the origins of mutations, advancing cancer and aging research.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Accumulated mutations drive cancer and genetic diseases.
  • Most mutations originate as single-strand DNA events, often missed by current sequencing.
  • Understanding these initial events is crucial for deciphering mutation origins.

Approach:

  • Developed a single-molecule, long-read sequencing technology.
  • Achieved single-molecule fidelity for single-base substitutions on both DNA strands.
  • Enabled detection of single-strand cytosine deamination events.

Key Points:

  • Defined the first single-strand mismatch and DNA damage signatures.
  • Linked single-strand signatures to known double-strand mutational signatures, identifying initiating lesions.
  • Observed distinct single-strand patterns in tumors with different repair deficiencies.

Conclusions:

  • The new method resolves the identity of initiating DNA lesions.
  • Provides insights into mutagenic mechanisms in the mitochondrial genome.
  • Enables new studies on mutation origins in cancer and aging at single-molecule resolution.