Local DNA structures and their importance in regulation of biological processes

5th March 2015

Versione stampabile

Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (TN) - Room B103
 at 2:30 p.m.

  • Václav Brázda, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic

Genome sequencing brings a huge amount of information regarding the genetic basis of life. While this information provides a foundation for our understanding of biology, it has become clear that the DNA code alone does not hold all the answers. Epigenetic modifications and higher order DNA structures beyond the double helix contribute to basic biological processes and maintaining cellular stability. Local alternative DNA structures are known to exist in all organisms. Negative supercoiling induces in vitro local nucleotide sequence-dependent DNA structures such as cruciforms, left-handed DNA, triplex and quadruplex structures etc. The formation of cruciforms requires perfect or imperfect inverted repeats of 6 or more nucleotides in the DNA sequence. Inverted repeats are distributed nonrandomly in the vicinity of breakpoint junctions, promoter regions, and at sites of replication initiation. Cruciform structures could for example affect the degree of DNA supercoiling, the positioning of nucleosomes in vivo, and the formation of other secondary structures of DNA. The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. The recognition of cruciform DNA seems to be critical not only for the stability of the genome, but also for numerous, basic biological processes. As such, it is not surprising that many proteins have been shown to exhibit cruciform structure-specific binding properties. In addition to a well-defined group of junction-resolving enzymes, we have classified cruciform binding proteins into groups involved in transcription and DNA repair (PARP, BRCA1, p53, 14-3-3, etc), chromatin-associated proteins (DEK, BRCA1, HMG protein family, topoisomerases, etc), and proteins involved in replication (MLL, WRN, 14-3-3, helicases, etc). Within these groups are proteins indispensable for cell viability, as well as tumor suppressors, proto-oncogenes and DNA remodeling proteins. Even single nucleotide polymorphisms at inverted repeats located in promoter sites can influence cruciform formation, which might be manifested through altered gene regulation. A deeper understanding of the processes related to the formation and function of alternative DNA structures will be an important component to consider in the post-genomic era.