PhD defence by Alberto Carli

Computational and structural analysis of protein interactions at the DNA replication fork

Assessment Committee:
Associate professor Mads Lerdrup, Department of Cellular and Molecular Medicine, University of Copenhagen (Chairperson)
Dr Pablo Alcón, Aarhus University
Professor Katrin Paeschke, University Hospital Bonn

Supervisors:
Associate Professor Thomas Charles Richard Miller
Associate Professor Eva Kummer

Department:
Department of Cellular and Molecular Medicine

Graduate Programme:
Cellular and Genetic Medicine

Place:
Building 22, Room: SUND-ICMM-Bibliotek-22-1-29, Blegdamsvej 3B, 2200 København

Email address to gain access to the thesis: albertoc@sund.ku.dk 
You will either receive a copy of the thesis or be informed where you can read a physical copy.

Short description of the thesis:
Every time a cell divides, its entire genome must be copied with remarkable accuracy. This process depends on a network of proteins working in precise coordination, yet many of the interactions that regulate DNA replication are fleeting and beyond the reach of conventional experimental methods. This thesis uses AI-based structure prediction combined with structural modelling and experimental validation to uncover these mechanisms. The application of this framework reveals how specialised enzymes are recruited to the replication machinery via short interaction motifs, with disruption of these motifs compromising genome stability. The approach extends to cancer-associated mutations and DNA damage bypass, offering a broadly applicable strategy for decoding the transient interactions that safeguard our genomes.