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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Protein | Definition | Taxonomy |
---|---|---|
ATP-dependent DNA helicase DinG | An ATP-dependent DNA helicase DinG that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P27296] | Escherichia coli K-12 |
Werner syndrome ATP-dependent helicase | A bifunctional 3-5 exonuclease/ATP-dependent helicase WRN that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14191] | Homo sapiens (human) |
Bloom syndrome protein | A RecQ-like DNA helicase BLM that is encoded in the genome of human. [PRO:DNx, UniProtKB:P54132] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
Telomestatin | 1,3-oxazoles | ||
1-(3,4-dichlorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea | ureas | ||
1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea | ureas |