Chimie Analytique Pharmaceutique : Libre Accès
Libre accès

Abstrait

Structural Biology: Recent Advances & Innovations In vivo enzymology to reveal a key mechanism to maintain genome integrity

Beata G. Vertessy

Preservation of genome integrity is of utmost importance for all living organisms. Several fine-tuned mechanisms have evolved to deal with DNA damages, which may arise not just from exogenous damaging agents but also under normal physiological conditions. DNA chemical modifications induced by various effects are highly numerous and diverse. Among these, modified bases often lead to mutations. We focus on the uracil moieties that can occur in the genome via cytosine deamination and thymine replacing misincorporations. The enzyme families involved in preventing the occurrence of the uracil mistake or excising the uracil base from DNA are investigated using a complex toolbox of structural, molecular and cell biology. High-resolution structures combined with in-depth functional analysis are also paired with transgenic models where specific mutations or other perturbations are introduced to assess in vivo structure and function. Models include human cell lines of various genetic origins, as well as Drosophila, zebrafish and mouse transgenic strains.