Telomeres play an important role in cellular aging and cancer. Human
telomeric DNA and RNA G-rich sequences are capable of forming a four-stranded structure, known as the G-quadruplex. Such a structure might be
important for telomere biology and a good target for drug design.
Thermodynamic and kinetic studies complement high-resolution structures
of G-quadruplexes. Such studies are essential for a thorough understanding
of the mechanisms that govern quadruplex folding and conformational
changes in quadruplexes.
This study examines the characteristics of binding of berberine to the
human telomeric d[AG3(T2AG3
)3] quadruplex. By employing UV-visible
spectroscopy, fluorescence spectroscopy and isothermal titration calorime-try, we found that the binding affinity of berberine to the human telomeric
quadruplex is 10
Tham khảo luận văn - đề án 'báo cáo khoa học: dna g-quadruplex: structure, function and human disease ´ ´ jaime gomez-marquez', luận văn - báo cáo, báo cáo khoa học phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả
Four-stranded G-rich DNA structures called G-quadruplexes have been
the subject of increasing interest recently. Experimental and computational
techniques have been used to implicate them in important biological pro-cesses such as transcription and translation.
Alternate DNA structures that deviate from B-form double-stranded DNA
such as G-quadruplex (G4) DNA can be formed by sequences that are
widely distributed throughout the human genome. G-quadruplex secondary
structures, formed by the stacking of planar quartets composed of four
guanines that interact by Hoogsteen hydrogen bonding, can affect cellular
DNA replication and transcription, and influence genomic stability.
G-quadruplex motifs constitute unusual DNA secondary structures formed
by stacking of planar hydrogen-bonded G-tetrads. Recent genome-wide
bioinformatics and experimental analyses have suggested the interesting
possibility that G-quadruplex motifs could be cis-regulatory elements.
Guanine-rich DNA sequences have the ability to fold into four-stranded
structures called G-quadruplexes, and are considered as promising antican-cer targets. Although the G-quadruplex structure is composed of quartets
and interspersed loops, in the genome it is also flanked on each side by
The Ewing’s sarcoma (EWS) oncogene contains an N-terminal transcrip-tion activation domain and a C-terminal RNA-binding domain. Although
the EWS activation domain is a potent transactivation domain that is
required for the oncogenic activity of several EWS fusion proteins, the nor-mal role of intact EWS is poorly characterized because little is known
about its nucleic acid recognition specificity.
Over the past few decades, numerous small molecules have been designed
to specifically and selectively target the unusual secondary structure in
DNA called the G-quadruplex. Because these ligands have been shown to
selectively inhibit the growth of cancer cells, they have become a central
focus for the development of novel anticancer agents.
The 3¢-ends of human chromosomal DNA terminate in short single-stranded guanine-rich tandem-repeat sequences. In cancer cells, these are
associated with the telomere-maintenance enzyme telomerase together with
the end-binding protein hPOT1.
The innate immune response of insects includes induced expression of genes
encoding a variety of antimicrobial peptides. The signaling pathways that
stimulate this gene expression have been well characterized by genetic analy-sis in Drosophila melanogaster, but are not well understood in most other
The presence and biological importance of DNA secondary structures in
eukaryotic promoters are becoming increasingly recognized among chemists
and biologists as bioinformatics in vitro and in vivo evidence for these
structures in the c-Myc, c-Kit, KRAS, PDGF-A, hTERT, Rb, RET and
Homologous recombination is a very important cellular process, as it pro-vides a major pathway for the repair of DNA double-strand breaks. This
complex process is affected by many factors within cells. Here, we have
studied the effect of monovalent cations (K
, and NH4
) on the
outcome of recombination events, as their presence affects the biochemical
activities of the proteins involved in recombination as well as the structure
Naturally occurring G-rich DNA sequences that are able to form G-quad-ruplex structures appear as potential targets for anti-cancer chemotherapy,
and therefore play an important role in cellular processes, such as cell
aging, death and carcinogenesis.