Term
| What are the three big reasons that the repliosome makes few mistakes? |
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Definition
1. 5'->3' polymerization
2. 3'->5' exonucleolytic proofreading
3. Strand-directed mismatch repair |
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Term
| How does a protein or enzyme recognize that DNA coding is wrong? |
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Definition
| Typically by the shape of the double strand |
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Term
| What are the bacterial proteins of strand-directed mismatch repair? |
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Definition
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Term
| How does strand-directed mismatch repair work? |
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Definition
| The protein complex scans newly synthesized DNA looking for "kinks" indicative of mis-match. The complex then excises the mis-match. Polymerase III fills in the gap |
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Term
| In strand-directed mismatch how does the repair machinery know which strand is the newly synthesized one? |
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Definition
In bacteria: through methylation patterns (old strand will be methylated)
In humans: looks for nicks left by okazaki fragments (no clear idea as to how this recognition works in leading strands) |
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Term
| What is the clinical significance of strand-directed mismatch repair? |
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Definition
| The cause of Hereditary nonpolyposis colerectal cancer is a mutation that makes the human DNA repair machinery mis-fire |
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Term
| What is the most common form of spontaneous alteration to DNA? |
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Definition
Methylation of position 8 on guanine.
forms 8-oxoguanine and is repaired by OGG1 (one of the glycosylases) |
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Term
| What is the name of the family of enzymes that repair the simple spontaneous alterations of DNA? |
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Definition
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Term
| What are the 3 major processes that cause simple local changes in DNA? |
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Definition
Hydrolysis
Oxidation
Methylation |
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Term
| When does Depurination occur and what can happen after it occurs? |
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Definition
Depurination (the loss of a purine adenine or guanine) occurs when the purine gets hydrolyzed off of the DNA strand.
If the DNA repair machinery does not find the mistake before replication then one of the DNA strands will have a deletion mutation (missing one base) |
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Term
| When does the Deamination of Cytosine occur and what results from it? |
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Definition
The deamination of Cytosine is a hydrolosis reaction that changes Cytosine to a Uracil.
The result is that, upon replication, one of the DNA strands will have a substitution mutation |
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Term
| What is base-excision repair and how does it work? |
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Definition
The hallmark of base-excision repair is that it fixes one base
It works by:
1. Detecting improper bases (once again using the topography of the DNA) with glycosylase
2. Glycosylase excises bad nucleotide
3. AP Endonuclease and Phosophodiesterase chew the now empty sugar-phosphate
4. DNA polymerase then repairs the hole |
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Term
| What is nucleotide excision repair? |
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Definition
The repair of typically a long series of mutated DNA.
Mechanistically:
1. Endonuclease cuts damaged area
2. Helicase strips off damaged strand
3. Polymerase fills the gap
4. Ligase seals the nicks |
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Term
| What is the most common damage that needs repair by nucleotide excision repair? |
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Definition
| UV damage, causes pyrimidine dimers |
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Term
| What are the two mechanisms for repair of an accidental double strand break? Which is the most common? |
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Definition
nonhomologous end-joining: the more common of the two, the jagged ends are degraded by nucleases and then the strands are stuck back together
2. Homologous end-joining: very uncommon, the second chromosome is used as a template for repair |
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Term
| What is the clinical significance of double strand break repair? |
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Definition
BRCA2 is one of the genes tagged with breast cancer.
BRCA2 codes for proteins that aid in double strand break repair |
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Term
| What is the clinical significance of nucleotide excision repair? |
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Definition
| This repair machinery corrects damage caused by UV radiation, a fairly common event. Mutations that affect this machinery lead to a disease called Xeroderma Pigmentosum where UV damaged is not repaired and results in extensive damage. |
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