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Short Tandem Repeats of Single-Stranded (ATTCC)n in Neutrophil Extracellular Traps Bind Thrombin

GSE253483 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2025/05/29 Platform GPL24676
Summary
DNA-protein interactions play a pivotal role in a variety of cellular processes. Despite the considerable research dedicated to understanding these interactions, the specific role of single-stranded DNA (ssDNA) remains largely unexplored. Our study aimed to uncover the role of ssDNA in the interplay between neutrophil extracellular traps (NETs) and thrombin, a crucial enzyme involved in both blood clot formation and immune response. Using chromatin immunoprecipitation sequencing (ChIP-seq) and kethoxal-assisted ssDNA sequencing, we identified a specific short tandem repeat (STR) sequence, ss(ATTCC)n, that is highly enriched and forms an iI-motif structure crucial for its interaction with thrombin. We further observed that the binding affinity between ss(ATTCC)n and thrombin is increased under acidic conditions, a condition frequently linked to diseases such as cancer. Our findings not only shed light on the unexplored area of sequence-dependent ssDNA-protein interactions but also pave the way for targeted interventions in thrombosis and coagulation disorders.
Published in
Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis
Guo W, Huang S, Shao X et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40608679 · doi:10.1073/pnas.2418191122
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Also filed as BioProject PRJNA1065880 and SRA study SRP484302. Searching any of these in the dataset finder brings you back here.

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