Conformational rearrangement of 1,2-d(GG) intrastrand cis-diammineplatinum crosslinked DNA is driven by counter-ion penetration within the minor groove of the modified site.

The major structural aberrations of DNA induced by a cis-diammineplatinum (II) 1,2-d(GG) intrastrand cross-link (CPT) have been known for decades. To gain deeper insights into the structural dynamics of the sequence-dependent DNA distortions adjacent to the CPT adduct, we employed molecular modeling and molecular dynamics (MD) simulations. The structural dynamics of native (N-DNA) and cisPt 1,2-d(GG) crosslinked (CPT-DNA) in the form of symmetric 36 nt d(GTG*G*TG)●CACCAC) oligonucleotide duplexes is compared.

Modeling the interactions of the nucleotide excision repair UvrA(2) dimer with DNA.

The UvrA protein initiates the DNA damage recognition process by the bacterial nucleotide excision repair (NER) system. Recently, crystallographic structures of holo-UvrA(2) dimers from two different microorganisms have been released (Protein Data Bank entries 2r6f , 2vf7 , and 2vf8 ). However, the details of the DNA binding by UvrA(2) and other peculiarities involved in the damage recognition process remain unknown.

DNA interstrand cross-links induced by ionizing radiation: an unsung lesion.

The induction of DNA interstrand cross-links by ionizing radiation has been largely ignored in favour of studies on double-strand break formation and repair. At least part of the problem is technical; it is difficult to detect and quantify interstrand cross-links when the same agent forms both cross-links and single strand breaks because the detection of interstrand cross-links generally involves a denaturation step. Our group has studied the induction of interstrand cross-links following irradiation of DNA containing bromouracil at specific sites.

Gamma-radiation induced interstrand cross-links in PNA:DNA heteroduplexes.

Peptide nucleic acids (PNAs) efficiently hybridize with DNA and are promoted as versatile gene-targeting analytical tools and pharmaceuticals. However, PNAs have never been exploited as radiopharmaceuticals, and radiation-induced physicochemical modifications of PNA:DNA heteroduplexes have not been studied. Drug- and radiation-induced creation of covalent cross-links in DNA obstruct crucial cell survival processes such as transcription and replication and are thus considered genotoxic events with a high impact in anticancer therapies.

Probing the interactions of the solvated electron with DNA by molecular dynamics simulations: II. bromodeoxyuridine-thymidine mismatched DNA.

The interaction of solvated electrons (e(-)(aq)) with DNA results in various types of DNA lesions. The in vitro and in vivo sensitisation of DNA to (e(-)(aq))-induced damage is achieved by incorporation of the electron-affinity radiosensitiser bromodeoxyuridine (BUdR) in place of thymidine. However, in DNA duplexes containing single-stranded regions (bulged BUdR-DNA), the type of lesion is different and the efficiency of damage is enhanced.

Probing the interactions of the solvated electron with DNA by molecular dynamics simulations: bromodeoxyuridine substituted DNA.

Solvated electrons ((e-)(aq)) are produced during water radiolysis and can interact with biological substrates, including DNA. To augment DNA damage, radiosensitizers such as bromo-deoxyuridine (BUdR), often referred to as an "electron affinic radiosensitizer", are incorporated in place of isosteric thymidine. However, little is known about the primary interactions of (e-)(aq) with DNA.

Oxidation of 2'-deoxycytidine to four interconverting diastereomers of N1-carbamoyl-4,5-dihydroxy-2-oxoimidazolidine nucleosides.

Modification of 2'-deoxycytidine (dCyd) by hydroxyl radicals and direct ionization leads to the formation of various oxidation products, including dCyd 5,6-glycols, 5-hydroxy-2'-deoxycytidine, and ring fragmentation products. The mechanism of oxidation is complex and poorly understood. In the present work, we have prepared four cis- and trans-diastereomers of N1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine by bromination of dCyd followed by peroxidation of the resulting dCyd bromohydrins.

Dynamic conformational states of DNA containing T.T or BrdU.T mispaired bases: wobble H-bond pairing versus cross-strand inter-atomic contacts.

The dynamic structure of 11-mer DNA duplexes of different sequences with or without homopyrimidine (T.T, or BrdU.T) mismatches was studied by molecular dynamics (MD) simulations on a time scale from 200 ps to 1 ns.

Metallophthalocyanines photosensitize the breakdown of (hydro)peroxides in solution to yield hydroxyl or alkoxyl and peroxyl free radicals via different interaction pathways.

Interactions of organic peroxides (R'OOR) and hydroperoxides (R'OOH), including H2O2, with excited triplet and singlet state metallophthalocyanines (MPc, M = Zn, Al) have been studied by T-T absorption decay and fluorescence quenching. The ensuing photochemical processes result in decomposition of (hydro)peroxides as assessed by photo-EPR (electron paramagnetic resonance) and spin trapping. In argon-saturated apolar solutions and low MPc concentrations, alkoxyl free radicals (*OR) were identified as the primary products of (hydro)peroxide breakdown.