Many errors happened in the DNA replication process, like mismatches and abnormal hairpin structures. Being able to understand how single mismatch affects hairpin structural stabilities and how single mismatch on hairpin was identified is therefore important.

Common fragile sites (CFS) contain AT-rich sequences that tend to form hairpins on lagging strands in DNA replication, making them hotspots for chromosomal rearrangements in cancers. Here, we investigate the structural stability of the AT-rich CFS DNA hairpins with single G-T mismatch using magnetic tweezers. Strikingly, a single G-T mismatched base pair in the short CFS DNA hairpin gives a 38.7% reduction of the unfolding Gibbs free energy and a thousand-fold increase of the transition kinetics than a single G-C matched ba...[ Read more ]

Many errors happened in the DNA replication process, like mismatches and abnormal hairpin structures. Being able to understand how single mismatch affects hairpin structural stabilities and how single mismatch on hairpin was identified is therefore important.

Common fragile sites (CFS) contain AT-rich sequences that tend to form hairpins on lagging strands in DNA replication, making them hotspots for chromosomal rearrangements in cancers. Here, we investigate the structural stability of the AT-rich CFS DNA hairpins with single G-T mismatch using magnetic tweezers. Strikingly, a single G-T mismatched base pair in the short CFS DNA hairpin gives a 38.7% reduction of the unfolding Gibbs free energy and a thousand-fold increase of the transition kinetics than a single G-C matched base pair, which are deviated from the theoretical simulations. Our study reveals the unique features of CFS to provide profound insights into chromosomal instability and structure-specific genome targeting therapeutics for genetic disorder-related diseases.

Many kinds of cancers have reported being closely associated with DNA mismatches. A Platinum-based molecular probe has shown the ability to differentiate the mismatch DNA hairpin from match DNA with the change of emission color. To better understand the mechanism of Pt-mismatch DNA interaction, we utilized Surface-enhanced Raman Spectroscopy (SERS) to characterize the mismatch/match DNA hairpin interacted with Pt-complexes with great reproducibility and sensitivity. We revealed that both mismatch and match DNA could interact with PtCN2. While PtCN2 has a stronger interaction with CC mismatch DNA through forming Pt-N covalent bond. This work will provide insights on designing mismatch-diagnosis biosensor with colour-tuneable emission.