Bio Lecture 15 DNA Repair Flashcards
What are mutations?
Permanent changes in the DNA.
How are mutations passed on?
When the mutation happens in the germ (sex) cells.
What happens when mutations happen in somatic cells?
Can lead to cancer
What is exonuclease activity?
While synthesizing the new strand of DNA, DNA polymerase can take a step back and remove a mismatched base. This is done in the 3’-5’ direction.
What is strand-directed Mismatch Repair or MMR?
Fixes errors missed by DNA polymerase.
Takes place during replication.
Msh protein binds to a bulge, Mlh finds the nearest nick in the protein. Mlh degrades the DNA between the nic and the error. The gap is filled in by DNA polymerase and DNA ligase.
Issues with MMR can lead to what condition discussed in class?
Hereditary Non-polyposis Colon Cancer where few or no polyps lead to colon cancer development much faster than the normal form of this cancer.
What is base excision repair?
Single strand repair mechanism after replication.
Glycosylases scan the DNA for damaged bases from deamination events. When found, the glycosylase cleaves out the damaged base and leaves an AP (apurinic/apyrimidinic) site and an abasic sugar.
AP endonuclease cuts the backbone and exonuclease removes the abasic residue.
DNA polymerase fills in the missing nucleotide and DNA ligase fills in the nick.
Can be used for missing base repairs also.
What is nucleotide excision repair?
After replication.
Protein complexes scan for distortions in the double helix. These errors often include pyrimidine dimers with Thymine and Cysteine.
Nuclease cleaves the backbone in two places.
Helicase separates out the section not wanted.
DNA polymerase and ligase fill in the gap.
What repair mechanisms are used for single strand issues?
Exonuclease activity.
Site-directed Mismatch Repair MMR
Base excision repair
Nucleotide excision repair
What is non homologous end joining (NHEJ)?
When a double stranded break occurs, each strand uses the other as a template to complete as much as possible the missing pieces. DNA ligase seals the gap between them.
This, however, often removes some bases and can cause mutations.
What is homologous recombination (HR)?
Fixes a double break.
Ensures accurate repair by using a sister chromatid or homologous chromosome as a template.
During cell division and not replication when duplicated chromosomes haven’t yet separated.
How is breast cancer related to DNA repair?
BRCA1 and BRCA2 are proteins involved with double strand repair. Mutations in these genes are inherited and increase a woman’s likelihood of cancer by 40-80%.
What is deamination?
Removal of an amine group from a nucleotide base. Cytosine becomes uracil when deaminated. This is fixed by base excision repair.
What are the two bonds in a nucleotide when forming DNA?
Glycosidic bond between the sugar and the base.
Phosphodiester bond between the 3’ and 5’ carbons of adjacent nucleotides.
How does Base Hydrolysis damage DNA?
The glycosidic bond between the base and sugar can be spontaneously hydrolyzed and broken. This usually happens to purines in a process called depurination. Pyrimidines can also be hydrolyzed, but it happens much less often. This is repaired through base excision repair.
If not repaired, this can cause a deletion mutation.
