Mapping Dynamics and Activity at the Replication Junction

Event: SMBio25 West
Location: Palo Alto, CA

What an inspiring two days at SMBio25 West in Palo Alto! A huge thank you to the organizers, LUMICKS and Shannon Yan, for bringing together such a vibrant single-molecule community.

It was fantastic to hear how researchers are using single-molecule techniques to untangle complex biological challenges. I was particularly captivated by the keynote presentations, which took us on a journey from the history of optical tweezers to today's cutting-edge research from Steven Block, Carlos Bustamante, Patrick Sung, and Geeta Narlikar.

Amidst a lineup of distinguished PIs, I was honored to be one of the junior scientists selected to present my PhD research from Gijs Wuite's group at Vrije Universiteit Amsterdam.

My talk, "Mapping Dynamics and Activity at the Replication Junction," introduced our novel C-DAM method. We revealed the surprisingly dynamic nature of DNA polymerase, which rapidly exchanges at the replication fork, challenging the stable replisome paradigm. The C-DAM technology transforms optical tweezers from passive manipulators into active, super-resolution imaging platforms by synergistically integrating mechanical and fluorescence data.

The talk showcased two key discoveries enabled by C-DAM:

  1. DNA Polymerase Exchange Dynamics: Revealing the surprising autonomy and rapid exchange dynamics of viral DNA polymerases (Nature Communications 2024), challenging the static view of the replisome.

  2. SSB Displacement Mechanism: Capturing the active displacement of single-stranded DNA binding proteins by DNA polymerase (Nature Communications 2025), resolving a long-standing question in DNA replication.

I am immensely grateful for the years of guidance from my PhD supervisor, Gijs Wuite, and the support of my former colleagues at VU Amsterdam. A special thanks also to my current supervisor, Carlos Bustamante, and my colleagues Francesca Burgos Bravo, Shantanu Kadam, Chen Li, and Jason Weng for their invaluable feedback.

The smooth presentation, engaging discussions, and great connections with fellow scientists made this a truly rewarding experience. The "Bustamante family photo" and the wonderful dinner hosted by Steven Block were unforgettable highlights!