# Mechanisms of DNA Damage Recognition by UDG and PARP1 in the Nucleosome

## TL;DR

This paper explores how enzymes recognize DNA damage in the nucleosome, suggesting mechanical deformation helps in the repair process.

## Contribution

The study introduces a model showing mechanical deformation aids enzyme recognition of DNA damage in nucleosomes.

## Key findings

- Damage recognition by UDG and PARP1 requires strict conditions not met by random search.
- Mechanical deformation of DNA around defective sites may signal damage and speed up repair.
- Simulations were conducted on a whole nucleosome with damage at various positions.

## Abstract

The DNA base-excision repair (BER) pathway shares the second part of its enzymatic chain with the single-strand break (SSB) repair pathway. BER is initiated by a glycosylase, such as UDG, while SSBR is initiated by the multifunctional enzyme PARP1. The very early steps in the identification of the DNA damage are crucial to the correct initiation of the repair chains, and become even more complex when considering the realistic environment of damage to the DNA in the nucleosome. We performed molecular dynamics computer simulations of the interaction between the glycosylase UDG and a mutated uracil (as could result from oxidative deamination of cytosine), and between the Zn1-Zn2 fragment of PARP1 and a simulated SSB. The model system is a whole nucleosome in which DNA damage is inserted at various typical positions along the 145-bp sequence. It is shown that damage recognition by the enzymes requires very strict conditions, unlikely to be matched by pure 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.