三核苷酸重複序列 (Trinucleotide repeat, TNR) 的擴張是導致許多神經退化性疾病的原因，而三核苷酸重複序列通常會折疊成二級結構，如:髮夾型結構，因此會在 DNA 進行複製、重組和修復的過程時中斷蛋白質的運作機制，並且這也被認為是造成錯誤擴增序列的主要原因。
單股 DNA 結合蛋白 (Single-stranded DNA binding protein, SSB) 是能夠在上述過程中結合單股 DNA 的主要蛋白，同時可以解開二級結構的能力，在這裡，我們使用大腸桿菌 SSB (Escherichia coli SSB, EcoSSB) 和 CTG 重複序列作為模型系統，並利用單分子螢光共振能量轉移光譜學 (single-molecule fluorescence resonance energy transfer, smFRET) 來研究三核苷酸重複序列對單股 DNA 結合蛋白的載入和重新分佈之影響。我們發現，相對於隨機捲曲的單股 DNA，三核苷酸重複序列的髮夾型結構嚴重阻礙單股 DNA 結合蛋白的負載；另一方面，當單股 DNA 結合蛋白負載到含有 CTG 重複序列和短單股 DNA的末端時，其過程中大約歷經數十分鐘的中間態而最後達到反應平衡，最後平衡的結構仍具有高度動態的結構變化，這表明單股 DNA 結合蛋白可以部分解開 CTG 重複序列的髮夾型結構，並在其當中進行擴散以重新分佈。

Trinucleotide repeat (TNR) expansions are responsible for many neurodegenerative disorders. TNRs usually fold into secondary structures such as hairpins, which interrupt protein machinery during DNA replication, recombination, and repair processes, and are believed to be the primary cause for the error-prone expansion. Single-stranded DNA binding protein (SSB), an essential protein that binds single-stranded DNA (ssDNA) during the abovementioned processes, has been shown the capability of unwinding secondary structures.
Here, we use Escherichia coli SSB (EcoSSB) and CTG repeat sequences as a model system to investigate the influence of TNR hairpin structure for the SSB loading and redistribution, utilizing single-molecule fluorescence resonance energy transfer (smFRET) spectroscopy. We found that TNR hairpins severely impede the loading of SSB compared to random-coiled ssDNA. On the other hand, when EcoSSB is preloaded onto the assay containing CTG hairpin and a short ssDNA loading end, it reaches the equilibrated configuration through an intermediate state in the order of tens minutes. The equilibrated configuration is highly dynamic, suggesting EcoSSB can partially unwind CTG hairpin and diffuse along it.

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