telomeric G-quadruplex DNA binding

Definition

Target type: molecularfunction

Binding to telomeric G-quadruplex DNA structures, in which groups of four guanines adopt a flat, cyclic Hoogsteen hydrogen-bonding arrangement known as a guanine tetrad. The stacking of guanine tetrads results in G-quadruplex DNA structures in telomeres. [GOC:BHF, GOC:BHF_telomere, GOC:nc, PMID:16142245, PMID:9512530]

Telomeric G-quadruplex DNA binding involves the recognition and interaction of a protein with the unique structural features of G-quadruplex DNA, which is a non-canonical DNA structure formed by the stacking of guanine tetrads. These interactions play crucial roles in regulating telomere length, stability, and replication.

**Molecular Function of Telomeric G-quadruplex DNA Binding:**

**1. Telomere Length Regulation:**

* Telomeres are protective caps at the ends of chromosomes that prevent DNA degradation and fusion.
* G-quadruplexes form in telomeric DNA, and their presence can influence the activity of telomerase, the enzyme responsible for maintaining telomere length.
* Proteins that bind G-quadruplexes can act as positive or negative regulators of telomerase activity, influencing telomere length and cellular lifespan.

**2. Telomere Stability and Replication:**

* G-quadruplex structures can impede DNA replication, potentially leading to replication stress and genomic instability.
* Proteins that bind G-quadruplexes can modulate the stability of these structures, impacting replication fork progression and preventing DNA damage.
* Some G-quadruplex binding proteins can facilitate the unwinding of these structures, allowing for efficient replication.

**3. DNA Damage Response:**

* The formation of G-quadruplexes can trigger DNA damage signaling pathways.
* G-quadruplex binding proteins can act as sensors of these structures, recruiting DNA repair machinery to ensure genomic integrity.

**4. Transcriptional Regulation:**

* Telomeric G-quadruplexes can influence gene expression by altering the accessibility of DNA to transcription factors.
* Proteins that bind G-quadruplexes can modulate gene expression by either stabilizing or destabilizing these structures, impacting the recruitment of transcription factors.

**5. Cellular Senescence:**

* Telomere shortening is associated with cellular senescence, a state of irreversible growth arrest.
* Proteins that bind G-quadruplexes can influence telomere length and senescence, impacting cellular aging and lifespan.

**6. Cancer Development:**

* G-quadruplexes are potential targets for anti-cancer therapies.
* Some proteins that bind G-quadruplexes have been shown to inhibit telomerase activity and promote cancer cell death.

**7. Other Biological Processes:**

* G-quadruplexes are also found in other genomic regions besides telomeres, and proteins that bind these structures may have roles in gene regulation and other biological processes.

**Conclusion:**

The binding of proteins to telomeric G-quadruplexes is a crucial molecular event with multifaceted implications. These interactions play significant roles in telomere biology, replication, DNA damage response, gene expression, cellular senescence, and cancer development. Further research is necessary to fully understand the intricate mechanisms involved in G-quadruplex DNA binding and its biological consequences.'
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Proteins (3)

Compounds (3)