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Long-patch Base Excision Repair01:02

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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Nucleotide Excision Repair01:38

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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Related Experiment Video

Updated: Mar 20, 2026

Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
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Nucleosomes determine their own patch size in base excision repair.

Rithy Meas1, Michael J Smerdon1

  • 1School of Molecular Biosciences, Washington State University, Pullman, WA, USA.

Scientific Reports
|June 7, 2016
PubMed
Summary

Nucleosomes preferentially direct base excision repair (BER) towards short patch repair, incorporating only one nucleotide. This finding reveals how DNA packaging influences DNA repair pathway choice.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Base excision repair (BER) is crucial for repairing DNA damage.
  • BER involves short patch (SP) and long patch (LP) subpathways, differing in nucleotide incorporation.
  • The influence of nucleosomes on BER subpathway choice was previously unexamined.

Purpose of the Study:

  • To investigate how nucleosomes affect the selection between SP and LP BER subpathways.
  • To determine if nucleosomal structure biases DNA repair patch size.

Main Methods:

  • Development of an assay to distinguish between short (1 nt) and long (2-12 nt) repair patches in designed nucleosomes.
  • Utilized cell-free extracts and purified enzymes, including DNA polymerase β.
  • Analyzed repair of single-nucleotide gaps within nucleosome core DNA.

Main Results:

  • Nucleosomes significantly limit DNA polymerase extension during BER.
  • A strong preference for SP BER (1 nt incorporation) was observed for lesions within nucleosome core DNA.
  • DNA polymerase β was identified as the key enzyme in this nucleosome-directed SP BER.

Conclusions:

  • Nucleosomes act as regulators of DNA repair pathway choice.
  • The physical constraints of nucleosomes impose a bias towards short patch repair.
  • This study elucidates a novel mechanism by which DNA packaging influences genome stability.