Define: Telomerase
Telomerase maintains the length of telomere so that they will not get shortened each time they go through replication
As related to telomeres, what are “ALT” mechanisms (and what do they have to do with recombination)?
ALT mechanisms rebuild or maintain telomere length without using telomerase, and generally do so by recombining telomeres from different chromosomes.
What are intercalations?
Intercalations are flat, aromatic inserts in between bases in the DNA.
Explain excision repair
-Uses an endonuclease to recognize and remove a damaged part of a strand of DNA
- Uses DNA polymerase and ligase to fill in the gap, based on the other undamaged strand
- versatile
- only works if one strand is undamaged
p53
Regulates transcription of genes that halt the cell cycle and trigger apoposis
Which strand of the DNA is extended by telomerase?
The leading strand
What type of mutation might chemical chlorination of a guanine base lead to?
Chemical chlorination of a guanine base might lead to damage in the DNA, which can cause permanent substitutions between bases.
What does DNA photolyase do?
DNA photolyase is an enzyme involved in the direct reversal/ repair of thymine dimers using light energy.
What is a Holliday junction?
A Holliday junction is a 4 way junction in DNA that can mediate recombination.
What normal adult human cells express telomerase?
Somatic cells
What type of mutation do intercalations cause?
Frameshift mutations
What kind of DNA repair might a Holliday junction be involved with?
The Holliday junction is most likely involved with recombination repair
What is direct reversal of damage?
If a base has been altered (eg. by adding a methyl group), have an enzyme do the reverse chemical reaction
What is a possible medical use of telomerase inhibitors?
Telomerase inhibitors could be used in the treatment of cancer. Since telomerase works by not allowing telomeres to shrink with each replication, inhibiting it would cause telomeres to shrink or trigger apoptosis and cancer will die.
What are the 3 types of mutations?
Substitutions
Insertions/deletions
Thymine dimers
What advantage does excision repair have over recombination repair? What advantage does recombination repair have over excision repair?
Excision repair uses its template strand to repair the damage while recombination repair requires another undamaged double helix to take a good strand from.
Recombination repair is advantageous when both strands are damaged or missing because it is able to repair both strands while excision repair only works if you have one undamaged strand.
Rho-dependent termination (describe how it works)
rho-dependent termination: once part of an mRNA transcript has been made, rho protein recognizes and binds to a site on it while transcription is still going on, then slides down the mRNA molecule, “chasing” RNA polymerase. When RNA polymerase gets to a site that makes it pause (eg by forming a hairpin in the mRNA), then rho bumps it off. A key feature here is that termination still occurs at repeatable places at the end of the gene (dependent on the mRNA sequence being transcribed), and it also requires a protein to help the termination occur
How can telomerase be involved in cancer?
Telomerase maintains the length of telomere so that they will not get shortened each time they go through replication. So, since they can never shorten to the point of death, they will essentially keep on replicating forever without consequences. Cancer actually activates telomerase which is why cancer cells can keep on replicating without the consequence of death because the telomeres are maintained and never shorten.
What is an advantage and a disadvantage of the Ames test?
Advantage: it allows rapid screening of compounds for mutagenic effects
Disadvantages: it uses bacteria, which lack some metabolic features found in humans; it tests compounds at high concentrations over a short period, whereas we are most concerned about effects of long-term exposure at low concentrations.
Explain how p53 links the cell cycle and DNA repair.
p53 does not fix DNA itself, but it does help sense DNA damage and cause other DNA repair enzymes to be produced (ie transcribed/translated), and halts the cell cycle (ie DNA replication) until the damage can be repaired. If the damage is too bad (unrepairable), it will trigger apoptosis (cell death).