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Peer-reviewedCC BY-NC-ND 4.0Nature Communications

Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα

Abstract

Genomic DNA is packaged into chromatin through a fundamental repeating unit known as the nucleosome core particle. Chromatinized genomic DNA is constantly exposed to endogenous and exogenous stresses that result in DNA damage, which must be repaired to maintain genome stability. Single-strand breaks (SSBs) are a prevalent form of DNA damage that arise via the oxidation-induced disintegration of the sugar-phosphate backbone or as repair intermediates during base excision repair. DNA ligase IIIα (LigIIIα) is one of the primary enzymes responsible for repairing ligatable SSBs during the terminal step of single-strand break repair (SSBR) and base excision repair (BER). To date, a mechanistic description of how LigIIIα processes nicks within chromatin remains elusive. Here, we use a combination of biochemical assays, molecular dynamics simulations, and cryogenic electron microscopy to define the molecular basis of nick ligation in the nucleosome by LigIIIα, providing foundational insight into the terminal step of chromatin-based SSBR/BER.

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BibTeX
@article{boesch2026molecular,
  title = {{Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα}},
  author = {Daniel Boesch and Nadia Martin and Chantal Kontor and Ashlee Nguyen and Alan Tomkinson and Bennett van Houten and Natacha Gillet and Emmanuelle Bignon and Amy Whitaker and Tyler Weaver},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77207-7},
  url = {https://hal.science/hal-05756642v1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα
AU  - Daniel Boesch
AU  - Nadia Martin
AU  - Chantal Kontor
AU  - Ashlee Nguyen
AU  - Alan Tomkinson
AU  - Bennett van Houten
AU  - Natacha Gillet
AU  - Emmanuelle Bignon
AU  - Amy Whitaker
AU  - Tyler Weaver
PY  - 2026
DA  - 2026/09/02
JO  - Nature Communications
DO  - 10.1038/s41467-026-77207-7
UR  - https://hal.science/hal-05756642v1
AB  - Genomic DNA is packaged into chromatin through a fundamental repeating unit known as the nucleosome core particle. Chromatinized genomic DNA is constantly exposed to endogenous and exogenous stresses that result in DNA damage, which must be repaired to maintain genome stability. Single-strand breaks (SSBs) are a prevalent form of DNA damage that arise via the oxidation-induced disintegration of the sugar-phosphate backbone or as repair intermediates during base excision repair. DNA ligase IIIα (LigIIIα) is one of the primary enzymes responsible for repairing ligatable SSBs during the terminal step of single-strand break repair (SSBR) and base excision repair (BER). To date, a mechanistic description of how LigIIIα processes nicks within chromatin remains elusive. Here, we use a combination of biochemical assays, molecular dynamics simulations, and cryogenic electron microscopy to define the molecular basis of nick ligation in the nucleosome by LigIIIα, providing foundational insight into the terminal step of chromatin-based SSBR/BER.
SN  - 2041-1723
SN  - 2041-1723
ER  -