HOLLER, E and BAUER, R and BERNGES, F (1992) MONOFUNCTIONAL DNA-PLATINUM(II) ADDUCTS BLOCK FREQUENTLY DNA-POLYMERASES. NUCLEIC ACIDS RESEARCH, 20 (9). pp. 2307-2312. ISSN 0305-1048, 1362-4962
Full text not available from this repository.Abstract
The question of whether monofunctional DNA platinum(II) adducts block synthesis of DNA by purified DNA polymerases of different types and origin has been investigated by comparing the time dependence of synthesis arrest and of DNA adduct formation. Activated salmon testis DNA is used as a suitable substrate for DNA synthesis allowing to probe inhibition by platinum(II) monoadducts for the variety of inherent template-primers. Reaction amplitudes are related to defined mixtures of dichloro and chloroaqua platinum(II) complexes. It is found that (i) all investigated DNA polymerases seem arrested (100% efficiency) at bifunctional DNA adducts. (ii) human DNA polymerase-beta-bypasses most of the monofunctional lesions of the three platinum(II) complexes investigated. (iii) Klenow fragment is blocked by monoadducts with increasing efficiency in the order cis-diamminechloroaquaplatinum(II) (0%) < meso-[1,2-bis(2,6- dichloro-4-hydroxyphenyl)ethylenediamine] chloroaquaplatinum(II) (50%) < trans-diamminechloroaquaplatinum (II) (75%). (iv) Escherichia coli DNA polymerase I, Thermus aquaticus DNA polymerase, Physarum polycephalum DNA polymerase-alpha, and calf thymus DNA polymerase-alpha appear to be arrested by monoadducts. According to these examples, blocking efficiencies depend on the cis/trans-stereogeometry of fixation of the carrier ligands at platinum(II) residues, on the size/chemical nature of the platinum(II) carrier ligand and on the type/origin of DNA polymerase.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTITUMOR DRUG CIS-DIAMMINEDICHLOROPLATINUM(II); ESCHERICHIA-COLI; DEOXYRIBONUCLEIC-ACID; TRANS-DIAMMINEDICHLOROPLATINUM(II); REPLICATION; KINETICS; BINDING; ALPHA; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/54539 |
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