Theoretical Study of Light-Induced Crosslinking Reaction Between Pyrimidine DNA Bases and Aromatic Amino Acids

Attila Bende,Valer Toşa,Alex-Adrian Farcaş

doi:10.3389/fbioe.2021.806415

Abstract

Low-lying electronic excited states and their relaxation pathways as well as energetics of the crosslinking reaction between uracil as a model system for pyrimidine-type building blocks of DNA and RNA and benzene as a model system for aromatic groups of tyrosine (Tyr) and phenylalanine (Phe) amino acids have been studied in the framework of density functional theory. The equilibrium geometries of the ground and electronic excited states as well as the crossing points between the potential energy surfaces of the uracil–benzene complex were computed. Based on these results, different relaxation pathways of the electronic excited states that lead to either back to the initial geometry configuration or the dimerization between the six-membered rings of the uracil–benzene complex have been identified, and the energetic conditions for their occurrence are discussed. It can be concluded that the DNA–protein crosslinking reaction can be induced by the external electromagnetic field via the dimerization reaction between the six-membered rings of the uracil–benzene pair at the electronic excited-state level of the complex. In the case of the uracil–phenol complex, the configuration of the cyclic adduct (dimerized) conformation is less likely to be formed.

Highlights

The DNA of a living cell is continuously exposed to external influences, which can induce various forms of DNA damage
In the present work, considering the B–U and phenol–uracil model systems, the light-induced DNA–protein crosslinking (DPC) reaction was investigated based on the ωB97X-D3 and SCS-PBE-QIDH XC density functional theory (DFT) functionals as well as DLPNO-CCSD (T) coupled-cluster theory
The result obtained for the first excited-state relaxation pathway of B–U shows that the S1 state presents a spontaneous relaxation till it reaches the supramoleculartype (S0⊗S1)a conical intersection (CI) point, defined by the deformation of both uracil and benzene moieties, from which the B–U binary system slides almost randomly into either stacking or CAtype geometry

Summary

Introduction

The DNA of a living cell is continuously exposed to external influences, which can induce various forms of DNA damage. E.g., appears as a covalent bond of proteins with a DNA strand, through either DNA bases or the sugar–phosphate chain, this phenomenon is called DNA–protein crosslinking (DPC). This is one of the most deleterious forms of DNA damage, which can disturb or even stop the proper cell transcription and replication. DPCs can be induced by exposure to various physical and chemical agents including ionizing radiation, UV light, transition metal ions, environmental contaminants, and common anticancer drugs (Connelly and Leach, 2004; Barker et al, 2005; Ide et al, 2011; Tretyakova et al, 2015). DPCs were first recognized as a distinct lesion in UV light-irradiated bacteria by Smith (Smith, 1962) and by Photocrosslinking Between DNA and Proteins

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