Elettra-Sincrotrone Trieste, Italy
Title: Integrative approaches to study the structure and motions of DNA sliding clamps
Biography: Alfredo De Biasio
Sliding clamps encircle DNA and tether polymerases and other proteins to the genomic template, and are essential factors in DNA replication. Because of the transient interaction that the clamps establish with DNA, the clamp-DNA interface eluded a thorough structural characterization, so that the molecular mechanism for clamp sliding on DNA remained obscure. Here, I will show how the combined use of high-resolution techniques (X-ray crystallography and NMR) and molecular dynamics (MD) simulations allowed to visualize the interactions between the Proliferating Cell Nuclear Antigen (PCNA) – the eukaryotic sliding clamp – and DNA, and to decipher the mechanics of sliding. In addition, recent findings show that the DNA sliding surface of PCNA can be modified to regulate the resistance to DNA damage. From a structural viewpoint, I will reflect on these findings which open a new perspective on PCNA function and offer opportunities to develop tools to manipulate the DNA damage response in cancer treatment.
1. De March, M. et al. Structural basis of human PCNA sliding on DNA. Nat. Commun. 8, 13935 (2017).
2. De Biasio, A. et al. Structure of p15PAF‒PCNA complex and implications for clamp sliding during DNA replication and repair. Nat. Commun. 6, 6439 (2015).