Binding of mismatch repair protein MutS to mispaired DNA adducts of intercalating ruthenium(II) arene complexes
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- DNA Adducts chemistry drug effects MeSH
- Anthracenes chemistry MeSH
- Base Pair Mismatch * drug effects MeSH
- Cymenes MeSH
- DNA chemistry drug effects MeSH
- Escherichia coli chemistry MeSH
- Ethylenediamines chemistry MeSH
- Intercalating Agents chemistry pharmacology MeSH
- Molecular Structure MeSH
- Monoterpenes chemistry MeSH
- Organometallic Compounds chemistry pharmacology MeSH
- DNA Damage MeSH
- Ruthenium chemistry MeSH
- Base Sequence MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- MutS DNA Mismatch-Binding Protein chemistry drug effects MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 4-cymene MeSH Browser
- DNA Adducts MeSH
- Anthracenes MeSH
- Cymenes MeSH
- DNA MeSH
- Ethylenediamines MeSH
- ethylenediamine MeSH Browser
- Intercalating Agents MeSH
- Monoterpenes MeSH
- Organometallic Compounds MeSH
- Ruthenium MeSH
- MutS DNA Mismatch-Binding Protein MeSH
The present study was performed to examine the affinity of Escherichia coli mismatch repair (MMR) protein MutS for DNA damaged by an intercalating compound. We examined the binding properties of this protein with various DNA substrates containing a single centrally located adduct of ruthenium(II) arene complexes [(eta(6)-arene)Ru(II)(en)Cl][PF(6)] [arene is tetrahydroanthracene (THA) or p-cymene (CYM); en is ethylenediamine]. These two complexes were chosen as representatives of two different classes of monofunctional ruthenium(II) arene compounds which differ in DNA-binding modes: one that involves combined coordination to G N7 along with noncovalent, hydrophobic interactions, such as partial arene intercalation (tricyclic-ring Ru-THA), and the other that binds to DNA only via coordination to G N7 and does not interact with double-helical DNA by intercalation (monoring Ru-CYM). Using electrophoretic mobility shift assays, we examined the binding properties of MutS protein with various DNA duplexes (homoduplexes or mismatched duplexes) containing a single centrally located adduct of ruthenium(II) arene compounds. We have shown that presence of the ruthenium(II) arene adducts decreases the affinity of MutS for ruthenated DNA duplexes that either have a regular sequence or contain a mismatch and that intercalation of the arene contributes considerably to this inhibitory effect. Since MutS initiates MMR by recognizing DNA lesions, the results of the present work support the view that DNA damage due to intercalation is removed from DNA by a mechanism(s) other than MMR.
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