Aklaylators and DNA Repair Flashcards
(34 cards)
What is Topoisomerase II (TOP2)?
TOP2 is a target of several important classes of anticancer drugs, including the anthracycline doxorubicin.
How do anticancer drugs like doxorubicin affect cancer cells?
These drugs kill cancer cells by trapping TOP2 in an enzyme intermediate termed the covalent complex with DNA, causing DNA strand breaks.
How does the body respond to DNA damage caused by anticancer drugs?
The body repairs this DNA damage using special repair pathways.
What is a major side effect of anthracyclines like doxorubicin?
Cardiotoxicity (heart damage) is a major side effect, but the exact cause is unclear.
What is another risk associated with anticancer drugs like doxorubicin?
Another risk is the development of secondary cancers due to drug-induced DNA changes.
What are scientists exploring as a potentially safer cancer treatment option?
Scientists are exploring catalytic inhibitors of TOP2.
What is the mechanism of DNA Intercalation by Doxorubicin?
Doxorubicin slips between (intercalates into) DNA base pairs, disrupting the DNA helix structure and blocking essential enzymes like topoisomerase II, which is needed for DNA replication and transcription.
How does Doxorubicin inhibit Topoisomerase II?
Doxorubicin stabilises the complex between DNA and topoisomerase II after the DNA has been cut but before it is resealed, causing permanent double-strand DNA breaks, leading to apoptosis (cell death).
What role do free radicals play in the action of Doxorubicin?
Doxorubicin undergoes redox cycling to produce negative oxygen species (ROS) like superoxide radicals, which can damage cellular components (especially DNA, lipids, and proteins), contributing further to cancer cell death.
What is telomerase?
Telomerase is an enzyme that adds repeated DNA sequences (‘TTAGGG’) to the ends of chromosomes (telomeres) to protect important DNA from being lost.
What happens to telomeres without telomerase?
Without telomerase, telomeres shorten every time a cell divides, eventually causing the cell to age and stop dividing.
What is the activity level of telomerase in most normal body cells?
In most normal body cells, telomerase is inactive or very low, so telomeres shorten with age.
In which types of cells is telomerase active?
Telomerase is active in stem cells and germ cells to allow many divisions.
How does telomerase function in cancer cells?
In cancer cells, telomerase is often reactivated, allowing cells to divide indefinitely, which is one reason cancer cells are immortal.
What are G-quadruplexes?
Stable DNA structures that can form in telomeres or gene promoters.
What roles do G-quadruplexes play?
They regulate gene expression, protect chromosome ends, control DNA replication and repair, and act as drug targets.
How do G-quadruplexes protect chromosomes?
They inhibit telomerase, the enzyme which cancer cells use to maintain their immortality.
Why is telomerase a target for cancer therapy?
Inhibiting telomerase is a potential anticancer strategy because cancer cells rely on it to keep dividing.
How can G-quadruplexes be targeted for cancer therapy?
By stabilizing these structures with drugs, telomerase activity is inhibited, making them a promising anticancer target.
What are G-quadruplexes?
G-quadruplexes can form in DNA regions rich in guanine such as telomeres and gene promoters (especially those with purine-rich strands).
What controls the formation of G-quadruplexes?
A balance exists between regular double-stranded DNA and G-quadruplexes, influenced by helicases and chaperone proteins.
What role do helicases play in G-quadruplexes?
Helicases are enzymes that unwind G-quadruplexes.
What role do chaperone proteins play in G-quadruplexes?
Chaperone proteins help G-quadruplexes form.
