Structural basis for UDG identifying DNA damage in the nucleosome
Ghediri, S.; Blossey, R.; Cleri, F.
Show abstract
The DNA base-excision repair (BER) pathway is initiated by a glycosylase, such as UDG, which identifies and removes a wrong base incorporated in the DNA sequence. The very early steps in the identification of the DNA damage are crucial to the correct initiation of the repair chain, and become even more complex when considering the realistic environment of damage to the DNA in the nucleosome. We performed all-atom docking and molecular dynamics computer simulations of the interaction between the glycosylase UDG and a mutated uracil. The model system is a whole nucleosome in which DNA damage is inserted at various positions along the 145-bp sequence. It is shown that damage recognition by UDG requires very strict structural conditions, unlikely to be matched by purely random search along the DNA. We propose that mechanical deformation of the DNA around the defective sites may help signaling the presence of the defect, accelerating the search process.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Optimising Elastic Network Models for Protein Dynamics and Allostery: Spatial and Modal Cut-offs and Backbone Stiffness 94%
- Structure-Based Classification of CRISPR/Cas9 Proteins: A Machine Learning Approach to Elucidating Cas9 Allostery 93%
- Allosteric hotspots in the main protease of SARS-CoV-2 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.