Term
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Definition
| semi-conservative replication (both strands of DNA replicated simultaneously) |
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Term
| Events that occur at replication fork |
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Definition
1. Priming by DNA primase (a DNA-dependent RNA polymerase)
2. Continuous & discontinuous DNA synthesis by DNA polymerase occurs on leading and lagging strands respectively
3. Okazaki fragments on lagging strand approx. 1000 bases (1 kb) long in prokaryotes
4. Elimination and replacement of RNA primers by equivalent DNA sequence
5. Ligation of DNA to connect the Okazaki fragments |
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Term
| Roles of DNA polymerases in prokaryotes |
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Definition
| Pol III does both leading and lagging strand synthesis. Pol I fills in the gaps |
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Term
| How are Okazaki fragments connected in prokaryotes |
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Definition
DNA polymerase I has both 5’-3’ polymerase (DNA) and 5’3’ exonuclease (RNA) activities, which act together to leave a “nick” in the DNA (b/c closing nick would require a 3’ to 5’ linkage).
DNA ligase links a free 5’ phosphate with a free 3’-OH at the “nick” to make a phosphodiester linkage and therefore create a continuous DNA strand |
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Term
| Function of topoisomerases |
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Definition
| cut the DNA strands to allow free rotation, and then rejoin them after the tension is released |
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Term
| Types of drugs that inhibit activity of topoisomerases |
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Definition
| Antibacterials such as quinolones and anticancer chemotherapeutics such as etoposide. The cut DNA cannot be rejoined so treated cells self-destruct during replication |
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Term
| Explain DNA polymerase proofreading and why it exists |
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Definition
Virtually all DNA-dependent DNA polymerases carry proofreading activity (3’-5’ exonuclease) – this includes BOTH DNA polymerase I and DNA polymerase III because it is always important to correct errors of DNA synthesis.
Proofreading provides a logical explanation for why DNA synthesis requires a primer with a free 3’-OH end – all DNA polymerases must check the last nucleotide before they add the next one
Replication fidelity is increased by about 10,000-fold, but some errors may persist |
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Term
| Mismatch Repair (MMR) in prokaryotes |
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Definition
1. Mature prokaryotic DNA is typically post-replicationally methylated on A bases within the sequence ….GATC....(this does not occur in eukaryotes)
2. Immature DNA does not yet have this methylation “mark” and is therefore distinguishable
3. Mismatch repair in prokaryotes performed by DNA pol III – therefore the replisome likely involved via communication with “Mut” complex proteins |
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Term
| Why can the HIV genome mutate so rapidly? |
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Definition
| Because HIV reverse transcriptase does not have a 3'-5' exonuclease activity |
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Term
| Major players in eukaryotic DNA replication |
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Definition
| Leading strand polymerase is typically pol ε, lagging strand is usually pol δ. Primer synthesis performed by a DNA primase/pol α complex. Primer degradation performed by a specialized nuclease in the replisome complex. Both proofreading and mismatch repair increase fidelity greatly (as in prokaryotes) |
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Term
| Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer [HNPCC]) |
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Definition
| Colon cancer due to mutation in DNA mismatch repair gene Mut. Acts as autosomal dominant. |
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Term
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Definition
| Extends the 3'-end of lagging strand. It carries its own template of RNA. it extends the telomere, allowing normal lagging strand synthesis via Okazaki fragments to continue. |
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Term
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Definition
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Term
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Definition
UGA (U Go Away)
UAG (U Are Gone)
UAA (U Are Away) |
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Term
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Definition
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Term
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Definition
| a change that specifies the same aa |
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Term
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Definition
| a change that specifies a different aa |
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Term
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Definition
| a change that produces a STOP codon |
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Term
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Definition
| an addition or loss of one or more bases that can lead to a translational frameshift |
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Term
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Definition
| Arise from complete absence or reduced amounts of normally functioning globin proteins |
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Term
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Definition
| Usually frameshifts bring new “stop” codons into play at some point downstream of the base insertion (or deletion) site, resulting in translated proteins with greater or lesser amounts of incorrect sequence. If the frameshift occurs early in the gene, the encoded protein will probably be inactive. If the frameshift occurs late in the sequence, the encoded protein may show some level of activity |
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Term
| Types of spontaneous DNA alterations |
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Definition
| depurination and deamination |
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Term
| basic mechanism of Base Excision Repair (BER) |
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Definition
| A single endonuclease strand cut occurs on the 5’ side of the “abasic” (loss of base) site. A small number of nucleotides (≥1) are eliminated by 5’-3’ exonuclease action. Base excision repair of DNA occurs in both prokaryotic and eukaryotic cells |
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Term
| What repairs depurinations and deaminations? |
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Definition
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Term
| basic mechanism of Nucleotide Excision Repair (NER) |
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Definition
| In NER, endonuclease cuts occur on both sides of the damage. Several proteins are recruited as part of the NER complex – each plays a crucial role. |
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Term
| post-DNA replication repair processes |
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Definition
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Term
| DNA replication-associated repair |
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Definition
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Term
| Clinical info of Xeroderma Pigmentosum |
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Definition
| Acute sun sensitivity, excessive freckling, hyperpigmentation, multiple primary cancers. The only treatment is protection from UV (of limited effectiveness). There is a 1000X risk of cutaneous cancer (<20 yrs) - median age of non-melanoma skin cancer is 8 yrs |
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Term
| Cause of Xeroderma Pigmentosum |
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Definition
| Defect in Nucleotide Excision Repair |
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Term
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Definition
| genetic term that signifies the ability of a particular gene to rescue a defect in a cell caused by a mutation. |
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