G-quadruplex DNA unwinding

Definition

Target type: biologicalprocess

The process by which G-quadruplex (also known as G4) DNA, which is a four-stranded DNA structure held together by guanine base pairing, is unwound or 'melted'. [GOC:jl, GOC:se, PMID:23657261]

G-quadruplex DNA unwinding is a complex process involving the disruption of the unique four-stranded structure formed by guanine-rich DNA sequences. This structure, known as a G-quadruplex, is stabilized by Hoogsteen hydrogen bonds between guanine bases, forming planar tetrads. The unwinding process can be initiated by various factors, including:

* **Ligand binding:** Specific molecules, such as small molecules or proteins, can bind to the G-quadruplex and destabilize its structure, promoting unwinding. These ligands often target the G-quadruplex groove or intercalate between its tetrads.
* **Helicases:** These enzymes are specialized proteins that utilize ATP hydrolysis to unwind DNA. Some helicases have been shown to specifically target and unwind G-quadruplex structures.
* **pH changes:** The stability of G-quadruplexes is sensitive to pH, and changes in pH can promote unwinding.
* **Ionic strength:** The presence of ions, particularly monovalent cations like potassium, can stabilize G-quadruplex structures. However, changes in ionic strength can also disrupt the stability and promote unwinding.

The mechanism of G-quadruplex unwinding is still under investigation, but several models have been proposed. One model suggests that unwinding proceeds through a series of intermediate states, with the G-quadruplex gradually unfolding into a single-stranded DNA. Another model proposes that the G-quadruplex can be directly converted into a double-stranded DNA, bypassing the single-stranded intermediate.

G-quadruplex unwinding has significant implications for various cellular processes, including:

* **Gene regulation:** G-quadruplexes can form in gene promoter regions, affecting gene transcription. Unwinding of these structures can influence gene expression.
* **DNA replication:** G-quadruplexes can obstruct DNA replication machinery, and unwinding is essential for the replication process.
* **Telomere maintenance:** G-quadruplexes are present in telomeres, the protective caps at the ends of chromosomes. Unwinding of telomeric G-quadruplexes may be involved in telomere replication and stability.

Further research is needed to fully understand the molecular mechanisms of G-quadruplex unwinding and its biological roles.'
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Proteins (3)

Compounds (3)