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Volume 10, Issue 8 (Suppl)

J Proteomics Bioinform, an open access journal

ISSN: 0974-276X

Structural Biology 2017

September 18-20, 2017

International Conference on

Structural Biology

September 18-20, 2017 Zurich, Switzerland

Integrative approaches to study the structure and motions of DNA sliding clamps

Alfredo De Biasio

Elettra-Sincrotrone Trieste, Italy

liding 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.

Biography

Alfredo De Biasio has work focus on the structure and function of DNA sliding clamps and their complexes operating in DNA replication and repair. He is particularly

interested in understanding the mechanisms of sliding of the eukaryotic clamp PCNA, and how these mechanisms are modulated by modifications of the PCNA

sliding surface, and the implications in DNA damage avoidance. These problems are tackled by an integrative approach that combines X-ray crystallography, NMR

and MD simulations.

alfredo.debiasio@elettra.eu

Alfredo De Biasio, J Proteomics Bioinform 2017, 10:8(Suppl)

DOI: 10.4172/0974-276X-C1-0100

Figure1:

PCNA is a ring-shaped trimeric protein that encircles DNA and binds the polymerases

during DNA replication and repair. The integrative use of structural and computational methods

allowed to describe the sliding mechanism of PCNA, a spiral motion that keeps the orientation

of PCNA relative to DNA invariant.