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27 Cards in this Set
- Front
- Back
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How accurate are DNA polymerases in replication?
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- 1 mistake every 10,000,000 bases inserted
- Polymerase fidelity 10-2 - 10-7 |
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Name polymerases in replication
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- Pol E (synthesis of leading strand)
- Pol d (synthesis of lagging strand) |
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Explain what happens in DNA polymerase active site
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- Entering nucleotide stabilized by 2 magnesiums (1 goes to alpha phosphate, and the other for the other 2), either an Arg or Lys also stabilizes the alpha phosphate. The 3'OH of the primer attacks the alpha phosphate of entering nucleotide.
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Number of lesions/day/person
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-3 x 1016
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Name two types of DNA damage
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- Spontaneous
- Induced |
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Name the three different DNA lesions
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- DNA strand breaks
- Base modifications - UV-induced dimers and crosslinks |
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DNA strand breaks characteristics
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- Single - repaired quickly, double lethal. Induced by ionizing radiation
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Base modifications characteristics
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- Base loss - Creates abasic site, non coding DNA
- Deamination - Oxidative Modifications - caused by ROS |
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UV-induced lesions characteristics
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- Dimers - TT blocks replication 100%
- Crosslinks - Linkage of two strands |
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Not repaired damage can lead to:
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- Mutations (base substitutions, large chromosomal rearrangements) and apoptosis.
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Name the 3 DNA repair pathways
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- Excision Pathways (BER, NER - non replicating DNA)
- Bypass Pathways (Recombination repair, translesion synthesis pathway - during replication) - Spellchecker Pathway (MMR - immediatly following replication) |
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BER characteristics
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- Removal of small base damage (methylation, oxidative damage) by glycosylase
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NER characteristics
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- Removal of big bulky DNA lesions (UV lesions, cisplatin). Large section is removed
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Defective NER leads to...
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- Xeroderma Pigmentosum
- Cockayne Syndrome - defective transcription-coupled NER |
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Defective MMR leads to...
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- Hereditary colorectal cancer
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Recombination Repair characteristics
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- Goes around the damage
- Uses the information from the other chromosome to bypass the damage |
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Defective Recombination Repair leads to...
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- Fanconi's Anemia
- Inherited Breast Cancer |
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Translesion synthesis characteristics
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- Uses special DNA polymerases with open structure that has reduced contacts with incoming nucleotide and primer (only 1 or 2 interacting sites instead of 40)
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Name all the TLS polymerases
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- Y family (Pol eta, iota, kappa, Rev1)
- B family (Pol zeta) |
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Pol eta characteristics
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- Low processivity (only 10 bases)
- Bypass of UV lesion TT - Its deficiency leads to XP syndrome |
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Pol zeta characteristics
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- Knockout leads to death of cell
- Can replace Pol eta but not with same efficiency |
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Rev 1 characteristics
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- dCTP transferase activity
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Pol iota characteristics
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- Low fidelity
- Favors hoogsteen bp - Role in BER |
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Pol kappa characteristics
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- Higher processivity
- Bypasses polycyclic aromatic hydrocarbons |
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Explain the two models of lesion bypass
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- Single polymerase model - Pol eta - insertion of all bases opposite to lesion, extension of damage primer lesion, 1 base beyond
- Two polymerase model - one pol iota inserts all bases opposite to lesion, second pol zeta extends damaged primer - Switches from TLS pol to normal - Gap filling after replication |
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Other proteins involved in Translesion Synthesis
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- PCNA - clamp holder
- Checkpoint proteins - work like PCNA - Replication machinery |
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What is somatic hypermutation?
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- Pol eta introduce mutations in genes, and produces genomic diversity during immune system development to select the B cell with highest affinity to antigen
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