Title:
Quantifying the Nanoscale Dynamics of DNA Processing Motors with Correlative Single-Molecule Methods
Abstract:
The dynamic interplay among DNA processing motors is critical for genome maintenance, yet direct observation of their real-time operation remains challenging. To address this, we developed Correlated Dynamics and Activity Mapping (C-DAM), a platform combining optical tweezers and confocal microscopy to simultaneously track protein position and enzymatic activity with high spatiotemporal resolution. Applying C-DAM to the DNA replication fork, we found that DNA polymerase undergoes rapid and autonomous exchange, which challenges the conventional model of a stable replisome. We further elucidated how the polymerase navigates roadblocks by actively and sequentially displacing single-stranded DNA-binding proteins (SSBs). These mechanistic insights advance our fundamental understanding of DNA replication. The developed methodologies also offer a potential framework for ‘single-molecule pharmacology,’ enabling future studies of drug-target interactions with unprecedented dynamic detail.
About the speaker:
Dr. Longfu Xu is a HHMI Fellow of the Damon Runyon Cancer Research Foundation at UC Berkeley, conducting postdoctoral research with Prof. Carlos J. Bustamante. He received his Ph.D. from VU Amsterdam, mentored by Prof. Gijs J.L. Wuite; both are pioneers in the field of single-molecule biophysics. His research lies at the intersection of biophysics, biochemistry, and molecular biology, where he develops cutting-edge correlative single-molecule techniques to probe the fundamental mechanisms of DNA processing motors essential for genome integrity. His work, highlighted in two first-author Nature Communications publications, has uncovered novel dynamic behaviors of the DNA replication machinery. Dr. Xu is a frequent speaker at major international conferences, sharing his mechanistic insights into protein-DNA interactions.
徐龙福博士，现为加州大学伯克利分校HHMI达蒙·鲁尼恩学者。他博士毕业于阿姆斯特丹自由大学，师从单分子生物物理学领域先驱Gijs J.L. Wuite教授；现博士后合作导师为该领域奠基人之一Carlos J. Bustamante教授。他的研究聚焦于生物物理、生物化学与分子生物学的交叉领域，致力于开发前沿的关联单分子技术，以探究维持基因组稳定性的DNA加工马达的核心工作机制。他的研究揭示了DNA复制机器全新的动态行为模式，相关成果以第一作者发表于两篇《自然·通讯》论文中。徐博士多次受邀在重要国际学术会议上作口头报告，汇报他对蛋白质-DNA动态互作的机制性见解。
报告时间地点：
时间：2025/11/28 09:00-10:00
地点：#腾讯会议：741-118-062
