Lecture 32 Flashcards
(50 cards)
What are the two categories of DNA repair mechanisms?
- repair of damaged bases
- repair of incorrectly base- paired bases during replication
What type of damage does X-ray and cancer drug do? What type of repair does it need?
double strand break; double strand repair
What type of damage does UV light do? What type of repair does it need?
Thymine dimer, bulky adduct; nucleotide excision repair
What type of damage does replication errors do? What type of repair does it need?
Base mismatch; mismatch repair
What type of damage does radiation, ROS, spontaneous hydrolysis? What type of repair does it need?
Depurination, cytosine deamination, single strand break, and base alkylation; base excision repair and direct reversal
What do environmental mutagens do?
- depurination
- deamination
- oxidation
- non-enzymatic methylation
What happens during long UV radiation?
It causes for DNA to form thymine dimers
How does a thymine dimer happen?
the result between two adjacent thymine residues forming two bonds (dimer) with each other
What is photolyase?
Repair the thymine dimers via direct repair or nucleotide excision repair by splitting the dimer and restoring the DNA
What is true about thymine dimer formation? Who forms it?
Lower eukaryotes not so much mammals
How can thymine dimers be repaired?
Direct repair mechanism by using photolyase. Also, nucleotide excision repair(NER)
How does photolyase work?
The photolyase enzyme binds to the DNA at the site of the thymine dimers in the dark. When visible light is present the enzyme breaks the bonds linking the pyrimidine rings, then the enzyme dissociates from the DNA in the dark.
What is NER?
A DNA repair mechanism also able to repair thymine dimers caused by UV light
What does NER apply to? What eukaryote uses it?
mammals
How does NER work?
The three-subunit UVrABC enzyme recognizes the thymine dimer as damaged DNA and with the help of ATP hydrolysis forces the DNA to bend. There is cleavage surrounding the damaged DNA on either side and the damaged DNA is removed. Polymerase and ligase replaces the damaged DNA with new DNA using the other strand (undamaged DNA) as a template
What happens if the NER pathway is deficient?
Can result in a rare genetic disease called Xeroderma Pigmentosa (XP)
What happens when nitrogenous bases are altered?
It can base pair with an incorrect base and result in a mis-pairing.
What is an example of a nitrogenous base getting altered? What happens?
If guanine gets altered by ionizing radiation or nitrosamines this will result in the guanine being changed to an oxidation of guanine (oxoG) or O6-methylguanine (O6-methylG).
What is found in food preservatives?
nitrosamines
What happens when oxoG or O6-methyl-G is formed? What does it bind to?
An oxoG can be mis-paired to an adenine, this DNA damage can be repaired via base excision repair. An O6-methylG can be mis-paired to a thymine, this DNA damage can be repaired via direct repair or base excision repair.
How can you fix O6-methylG?
Specific methyltransferase(direct repair). It recognizes methylG and cuts it away
What happens when O6-methyguanine is formed and forms residue?
It can lead to mutagenesis
How does AP site and base excision repair?
These enzymes can recognize a single damaged base and cleave the bond between it and the sugar in the DNA.
How does AP site and base excision repair work? How does it function?
Removes one base, excises several around it, and replaces with several new bases using Pol adding to 3’ ends then ligase attaching to 5’ end
