Enzymatic reaction with unnatural substrates: DNA photolyase (Escherichia coli) recognizes and reverses thymine [2+2] dimers in the DNA strand of a DNA/PNA hybrid duplex

Peptide nucleic acids (PNA) are mimics with normal bases connected to a pseudopeptide chain that obey Watson–Crick rules to form stable duplexes with itself and natural nucleic acids. This has focused attention on PNA as therapeutic or diagnostic reagents. Duplexes formed with PNA mirror some but not all properties of DNA. One fascinating aspect of PNA biochemistry is their reaction with enzymes. Here we show an enzyme reaction that operates effectively on a PNA/DNA hybrid duplex. A DNA oligonucleotide containing a cis, syn-thymine [2+2] dimer forms a stable duplex with PNA. The hybrid duplex is recognized by photolyase, and irradiation of the complex leads to the repair of the thymine dimer. This finding provides insight into the enzyme mechanism and provides a means for the selective repair of thymine photodimers.

肽核酸（peptide nucleic acids, PNA）是一类核酸碱基模拟物，其正常碱基连接于假肽链之上，可遵循沃森-克里克碱基配对规则，自身或与天然核酸形成稳定双链结构。这一特性使得肽核酸作为治疗或诊断试剂受到广泛关注。PNA形成的双链结构可部分模拟但并非完全复刻脱氧核糖核酸（DNA）的特性。肽核酸生物化学领域一个极具研究价值的方向，是其与酶类的相互作用。本研究展示了一种可有效作用于PNA/DNA杂合双链的酶促反应：含有顺式-同向胸腺嘧啶[2+2]二聚体的DNA寡核苷酸链，可与PNA形成稳定双链结构。该杂合双链可被光裂合酶识别，对该复合物进行辐照可实现胸腺嘧啶二聚体的修复。这一发现不仅为阐明酶促反应机制提供了新视角，也为胸腺嘧啶光二聚体的选择性修复提供了可行手段。