Question

An approach to reducing telomerase activity in tumor cells involves drugs that bind to G-quadroplex DNA since telomeres have the potential to form such structures. What is a G-quadroplex, and what about telomere structure might lead to it?

Short answer

Answer: A G-quadruplex, or G-quadroplex, is a secondary structure formed in nucleic acids like DNA or RNA when guanine (G) base pairs from different strands bond together to create guanine tetrads. The stacking of guanine tetrads, stabilized by potassium or sodium ions, results in a G-quadruplex structure. In telomeres, the protective sequences at the ends of chromosomes, the repeat sequence TTAGGG is abundant in guanine (G) bases, which allows for the formation of G-quadruplex structures. These structures can affect the function of telomeres and the activity of the enzyme telomerase, making G-quadruplexes potential therapeutic targets for inhibiting telomerase activity in cancer cells.

Step-by-step solution

Definition of G-quadroplex

A G-quadruplex (also referred to as a G4 structure or G-quadroplex) is a secondary structure of nucleic acids such as DNA or RNA that is formed when guanine (G) base pairs from different strands of the same nucleic acid molecule hydrogen bond to form square planar structures called guanine tetrads. Stacked guanine tetrads stabilized by potassium or sodium ions create a G-quadruplex structure.

Telomere structure

Telomeres are the protective sequences at the ends of chromosomes that consist of multiple repeats of a specific DNA sequence. In humans, the repeat sequence is TTAGGG, and it is repeated around 3000 times in every telomere. Telomeres prevent the degradation of chromosomes' coding sequences during replication, maintaining genomic stability and preventing cellular aging.

Formation of G-quadroplex in telomeres

Due to the abundance of guanine (G) bases in the telomeric sequence, telomeres have the potential to adopt G-quadruplex structures. The G-rich structure of telomeric DNA facilitates the formation of guanine tetrads, which can stack together to form a G-quadruplex structure. This G-quadruplex structure can influence the functions of telomeres, such as the activity of the enzyme telomerase.

G-quadroplex as a therapeutic target

Telomerase is an enzyme that helps maintain the length of telomeres by adding the repetitive TTAGGG sequence to the ends of chromosomes. This process is critical for the continuous division and infinite lifespan of cancer cells. Targeting G-quadruplex structures in telomeres can be a potential therapeutic approach to inhibit telomerase activity in cancer cells, thereby limiting their growth and division. By binding to these G-quadruplex structures, drugs can either stabilize or destabilize them, consequently affecting the activity of telomerase and potentially hindering cancer progression.