Báo cáo khoa học: DNA G-quadruplex: structure, function and human disease ´ ´ Jaime Gomez-Marquez doc

MINIREVIEW SERIES
DNA G-quadruplex: structure, function and human disease
Jaime Go
´
mez-Ma
´
rquez
Department of Biochemistry and Molecular Biology, Faculty of Biology-CIBUS, University of Santiago de Compostela (USC), Spain
The role of non-B DNA in the function and stability
of genomes has become generally appreciated in recent
years. It is now evident that DNA also encodes for
spatial structures that are involved in gene regulation,
replication and recombination.
There are several types of secondary structures in
non-B DNA. Among these noncanonical structures are
hairpins and cruciforms, intramolecular triplexes or
H-DNA, left-handed Z-DNA and guanine-rich repeats
which have the capacity to adopt G-quadruplex
(G4-DNA); the latter structure is also referred to in the
literature as G-tetraplex. G4-DNA consists of a hydro-
gen-bonded self-assembly of four guanine bases, paired
by Hoogsteen bonding, which forms planar arrange-
ments, the G-quartets. Charge coordination by mono-
valent cations stabilizes G-quartet stacking, resulting in
intramolecular or intermolecular association of four
DNA strands in a parallel or antiparallel orientation.
Genomes contain a high number of G-rich sequences
that could form G4-DNA and this structure may
serve important regulatory and structural functions; in
addition, it can be the source of genomic instability
which may lead to cancer, aging and human genetic dis-

eases. In silico analysis using different computational
methods, as well as laboratory experiments, indicates
that many G-rich regions of chromosomes – rDNA, sin-
gle-copy genes, recombination sites like those involved
in immunoglobulin class-switching and repetitive
sequences including satellite and telomeric DNA
sequences – have the potential to form G4-DNA struc-
tures. Interestingly, RNA is also capable of forming G4
structures even more stable than those of DNA. In this
sense, it is tempting to speculate that RNA G-quadru-
plexes could play a role in translation regulation, in a
manner analogous to G4-DNA and transcription. In the
human genome, the number of sites with the potential
to form G-quadruplex is surprisingly high. Some of
these sites are within genes and are potential threats to
genome stability because they can alter the DNA archi-
tecture and interfere with normal DNA processes, such
as replication and transcription.
Although G4-DNA has been rigorously studied
in vitro, whether this structure actually forms in vivo
and what its cellular roles might be, remains unclear.
However, recent advances have made a persuasive case
for the existence of G4-DNA in living cells and its par-
ticipation in the regulation of processes as varied as
telomere maintenance, transcription, recombination
and ribosome biogenesis.
This minireview series deals with the structural and
functional characteristics of G4-DNA, as well as its
implication in human disease. In the first minireview,
Huppert gives an introduction to the structure and

genomic distribution of putative G4-DNA-forming
sequences and creates a theoretical background for the
other two articles in the series. He discusses the com-
putational approaches used to predict them on a geno-
mic scale, and how the information derived can be
combined with experiments to understand their biolo-
gical functions.
In the second minireview, Brooks, Kendrick & Hurley
examine the diversity of G4 structures and i-motifs in
promoter elements and attempt to categorize the differ-
ent types of arrangements in which they are found.
The third minireview, by Wu & Brosh, provocatively
summarizes the presumed in vivo role of G4-nucleic
acid structures and discusses the consequences of
human genetic defects affecting the different enzymes
that manipulate G-quadruplex structures. They present
all the circumstantial evidence suggesting that G-quad-
ruplex nucleic acid structures, which have been demon-
strated unambiguously to be formed on specific
sequences in naked DNA in vitro, do exist in vivo in
the chromatin-embedded genomic DNA. Finally, they
discuss the connections of G-quadruplexes to human
genetic diseases and cancer.
Jaime Go
´
mez-Ma
´
rquez is Professor of Biochemistry and Molecular Biology at the Faculty of Biology of the Univer-
sity of Santiago de Compostela (USC), Spain (). In 1981, after obtaining his PhD in
the biochemistry laboratory at USC, he joined the National Institutes of Health (Bethesda, MD, USA) as a postdoc-

toral fellow to study the latency of HSV-1. Later, he investigated the molecular biology of prothymosin alpha and
beta-thymosins. His current research focuses on analysis of the structure, phylogenetic origin and function of
human minisatellite DNA. At present, he is investigating the role of G4-DNA in recombination.
doi:10.1111/j.1742-4658.2010.07757.x
FEBS Journal 277 (2010) 3451 ª 2010 The Author Journal compilation ª 2010 FEBS 3451