Title:Non-B DNA Structures as Candidate Drug Targets Against Structural Chromosomal Instability
Volume: 16
Issue: 2
Author(s): Nevim Aygun*
Affiliation:
- Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir,Turkey
Keywords:
Non-B DNA structures, repetitive DNA sequences, candidate drug targets, structural chromosomal
instability, cancer, genetic diseases.
Abstract: Background: Enzymes, proteins, receptors, ion channels and DNA/RNA are
among drug targets. DNA-interactive drugs involve alkylation (temozolomide,
chlorambucil and cyclophosphamide), intercalation (doxorubicin), DNA breakage
(nitroimidazoles), oxidative degradation (bleomycin), code-reading (polyamides and
triplex-forming molecules) and stabilization of topoisomerase-DNA complexes
(doxorubicin, etoposide, mitoxantrone and SN-38) and G-quadruplexes (perylene, cationic
porphyrins and telomestatin). As a non-B DNA structure, G-quadruplexes may form at
single-stranded 3'-overhangs of telomeres and the promoters of proto-oncogenes.
Telomeric and non-telomeric oligodeoxynucleotides in G-quadruplex conformation
exhibit antiproliferative activity against tumour cells and induce apoptosis. However, Gquadruplex
motifs are widespread around the chromosome translocation breakpoints in
lymphoid cancers.
Conclusion: Hairpin/cruciform or slipped-strand DNA structures extruded by inverted
and direct repeats, respectively, could be involved in the induction of translocations,
deletions, isochromosomes, duplications and inversions in human cancers and genetic
diseases as well as the expansion of short nucleotide repeats in hereditary neurological
diseases. In addition, there is a significant association between long inverted repeats
(LIRs) and the breakpoint regions of gross gene deletions in human cancers and inherited
diseases. Thus, this review will focus on non-B DNA structures as candidate drug targets
against structural chromosomal instability in various diseases.
