Primer-Like Inhibitors for DNA Repair Enzymes of the AML-HL60 and WERI-1A/Y79 Malignant Cells
Open Access
- 1 January 2019
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Advances in Enzyme Research
- Vol. 07 (03), 27-44
- https://doi.org/10.4236/aer.2019.73003
Abstract
A conventionally synthesized thio- and cyano-modified single-stranded poly(dNTP) sequences of different molecular sizes (20n - 200n) and the same lengths routine poly(dNTP) and poly(NTP) species were obtained through the good services provided by the Russian Federal Bioorganic Products Group and by the ThermoFischer, Inc., and then tested for their impact on catalytic activities of β-like DNA polymerases from chromatin of HL-60, WERI-1A and Y-79 cells as well as for the affinity patterns in DNApolβ-poly(dNTP)/ (NTP) pairs, respectively. An essential link between the lengths of ultrashort (50n - 100n) single-stranded poly(dNTP) sequences of different structures and their inhibitory effects towards the cancer-specific DNA polymerases β has been found. A possible significance of this phenomenon for both DNA repair suppression in tumors and a consequent anti-cancer activity of the DNA repair related short poly(dNTP) fragments has been for the first time emphasized with a respect to their pharmacophore revealing potential. Thus, this work presents an experimental attempt to upgrade a contemporary attitude towards the DNA derived products applied for anti-cancer agenda, particularly, for acute myeloid leukemia and retinoblastoma cell DNA repair machinery breakdown. In this study, tumor specific DNA polymerases β were found of being the targets for attack promoted with the primer-like single-stranded DNA fragments followed by consequent cytostatic phenomena. A novel concept of the DNA related anti-cancer medicines is under discussion.Keywords
This publication has 27 references indexed in Scilit:
- Resisting ResistanceAnnual Review of Cancer Biology, 2017
- Human single-stranded DNA binding proteins: guardians of genome stabilityActa Biochimica et Biophysica Sinica, 2016
- An Overview of DNA-Protein InteractionsCurrent Chemical Biology, 2016
- Systems biology of death receptor networks: live and let dieCell Death & Disease, 2014
- Human single-stranded DNA binding proteins are essential for maintaining genomic stabilityBMC Molecular Biology, 2013
- An Atypical DNA Polymerase Beta Overexpressed in Human Aml/Hl-60 Malignant CellsJournal of Cancer Science & Therapy, 2013
- The Mitochondria Free Iron Content to Limit an Isotope Effect of 25Mg2+ in ATP Synthesis: A cautionCell Biochemistry and Biophysics, 2012
- Simple, Non-radioactive Measurement of Single-Stranded DNA at Telomeric, Sub-telomeric, and Genomic Loci in Budding YeastMethods in molecular biology (Clifton, N.J.), 2012
- Ultramicro-analysis by Use of Light-Scanning Photoacoustic Densitometry for Electrophoresed Protein in Human HairAnalytical Biochemistry, 1996
- Influence of template inactivators on the binding of DNA polymerase to DNANucleic Acids Research, 1974