Biophysics Ph.D. Thesis Defense: Scott Berger, Monday, June 2, 2:30 PM, Munzer!
Dear CSB Friends,
We hope you can join us for an upcoming thesis defense!
STANFORD UNIVERSITY BIOPHYSICS PROGRAM
SPEAKER: Scott Berger
ADVISOR: Gheorghe Chistol
DATE: Monday, June 2nd
TIME: 2:30 – 3:30 PM
LOCATION: Munzer Auditorium
CELEBRATION:
TIME: 4:30 PM
LOCATION: CCSR Atrium
TITLE: On the Origins of Replication
ABSTRACT:
How do metazoan cells ensure that each replication origin gives rise to a pair of correctly assembled helicases? Despite decades of study, the molecular choreography that drives origin firing remains elusive, largely due to the transient and asynchronous nature of replication initiation. In this defense, I present single-molecule imaging to illuminate this process in real time. By visualizing key replication factors—including Cdc45, GINS, and DONSON—in Xenopus egg extracts, I reveal that replication initiation is far more dynamic than previously appreciated. Two copies of GINS and Cdc45 are recruited simultaneously to origins, despite the fact that neither protein dimerizes in vitro. This symmetry is enforced by protein scaffolds: DONSON delivers two GINS molecules, while Cdc45 likely relies on a yet-unidentified partner. In a complementary project, I explored how cells modulate the rate of DNA replication initiation in response to replication stress. Using the same real-time single-molecule imaging approach, I developed a system to precisely and acutely modulate ATR signaling in Xenopus extract. This revealed that ATR suppresses replication initiation through the CHK1 kinase, specifically by inhibiting helicase assembly. Although ATR/CHK1 are thought to respond to stress, I show both kinases are active in the absence of stress. Together, this work uncovers the dynamics of replication initiation and provide a clearer framework for understanding how metazoan cells regulate genome duplication under normal and stressed conditions.