Specific DNA sequences in Yeast species S. pombe can form four-stranded DNA : A Study
Researchers at Umeå University in Sweden have discovered that specific DNA sequences that are rich in the DNA building block guanine in the yeast species, Schizosaccharomyces pombe, can form four-stranded DNA. In a study published in the journal Nucleic Acids Research, the researchers also show that the motor protein Pfh1 can unfold these DNA structures and thus contribute to maintaining an intact genome.
DNA appears in different configurations in addition to the double strands coiled around each other. One of these forms consists of a guanine-rich four-stranded DNA, a so-called G4 structure.
G4 structures can present a threat if they exist continuously in the genome. Helicases are a type of specialized motor protein with the ability to unfold different kinds of DNA. Until now, there were very few studies about G4 structures in Schizosaccharomyces pombe, also known as fission yeast. It was also not known which protein is responsible for the unfolding of the G4 structures.
Research on G4 structures is at its early stage. But researchers believe that G4 structures can inhibit certain processes in the cells, including DNA replication, and have tied them to the
development of cancer and neurodegenerative diseases in humans. It is clear that the formation and elimination of G4 structures must be well-balanced to satisfy the cell’s needs and ensure its integrity.“By using different biochemical and biophysical methods, we show that specific DNA sequences from the Schizosaccharomyces pombe’s ribosomal and telomeric DNA regions have a strong tendency to form G4 structures,” says Nasim Sabouri, Assistant Professor at the Department of Medical Biochemistry and Biophysics, and one of the researchers in the study.
“Our cell biological analysis show that a helicase, called Pfh1, binds to specific guanine-rich DNA sequences in the yeast cell. We also show in biochemical experiments that Pfh1 has the ability to unfold G4 structures. An efficient unfolding of these structures is necessary in order to secure the integrity of the genome during DNA replication,” added Nasim Sabouri.
Nasim Sabouri is hopeful that the discovery would open doors for the treatment of cancer. “An interesting research area is the development of molecules with the specific ability to bind to and stabilize G4 structures. This could potentially be used to turn off the expression of certain genes that are involved in tumour formations. We are hopeful that our advancements in understanding of G4 structures could eventually facilitate the development of new drug treatments for cancer. This is something we would like to focus more on.”
