Abstract
Thio- and cyano- modified single-stranded poly(dNTP) sequences of different molecular sizes (20–200 n) and the same lengths routine poly(dNTP) and poly(NTP) species were 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 (50–100 n) single-stranded poly(dNTP) sequences of different structures and their inhibitory effects towards the cancer-specific DNA polymerases β was 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 is under discussion.
Highlights
A background-lying platform of this work derives from experimental data on magnetic isotope effects (MIE) towards both DNApolβ catalytic activity [1,2,3] and the viability of cancer cells [1,2].a sharp decrease of the survival ability patterns of 25 Mg2+ -treated AML/HL-60 cells as compared to abundant spineless, non-magnetic magnesium ions impact was found [1]
It was shown that a processivity of beta-like DNA polymerases isolated from the all abovementioned malignant cells depends on MIE, so the resulted DNA fragment sizes becomes shorter within a 40–250 n range following the increase of magnetic isotope content in a total metal pool [2,3]
An up to 58% elevation of 43 Ca2+ content leads to a monotonic decrease of sizes of polynucleotides processed from average 230–250 n to an abnormal (DNA repair invalid) 36–40 n as directed by beta-like DNA polymerases from Y-79 and WERI-1A retinoblastoma cells [1]
Summary
A background-lying platform of this work derives from experimental data on magnetic isotope effects (MIE) towards both DNApolβ catalytic activity [1,2,3] and the viability of cancer cells [1,2].a sharp decrease of the survival ability patterns of 25 Mg2+ -treated AML/HL-60 cells as compared to abundant spineless, non-magnetic magnesium ions impact was found [1]. An up to 58% elevation of 43 Ca2+ content leads to a monotonic decrease of sizes of polynucleotides processed from average 230–250 n to an abnormal (DNA repair invalid) 36–40 n as directed by beta-like DNA polymerases from Y-79 and WERI-1A retinoblastoma cells [1]. This nuclear–magnetic control over the DNA synthesis, allows a firm statement that a replication mechanism involves some ion–radical steps consisting of the ion–radical pairs formation [1] A similar result was obtained from the same leukemia cells treated with magnetic, nuclear spin possessing, 43 Ca2+ and 67 Zn2+ ions [1,3] as well as on human retinoblastoma cells subjected to these metal isotopes [2,3].
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