Medical Genetics Flashcards
How many hydrogen bonds are between each pair?
A-T: 2
C-G: 3
What are the major characteristics of B DNA?
- Right handed twist
- 2 Nm diameter
- 0.34 Nanometers btwn base pairs
- Each turn is 10 base pairs —> every 3.2 nm
*Human DNA
How does actinomyocin work?
Intercalating into the narrow groove of DNA double helix and interfering with synthesis of RNA
What is Theta replication?
Circular DNA (E. Coli) replication with a single origin and is bidirectional
Differentiate functions of the five polymerase enzymes.
DPIII - Performs DNA replication (Both 5-3/3-5)
DPI - Remove RNA primers Both 5-3/3-5 activity
DP II/IV/V - DNA repair
What is the primary function of Pol I?
Repair any damage with DNA and connect Okazaki fragments by deleting RNA primers and replacing with DNA
What are the four enzymatic activities of DPI?
- 5-3’ DNA-Dependant activity and require a 3’ primer site and template strand
- 3-5’ (Reverse) exonuclease which mediates proofreading
- 5-3’ exonuclease activity mediating nick translation during repair
- 5-3’ RNA-Dependant activity (Very limited due to low binding capacity)
What is the primary enzyme responsible for DNA replication?
DP III
What is the Klenow fragment?
- Large protein produced when DPI from E. Coli is enzymatically cleaved
- Retains activity of DPI except reverse exonuclease activity
- Used for: Double strains synthesis from templates, Digesting away 3’ overhangs, Preparing radioactive DNA probes, and Filling in receded 3’ DNA ends to make 5’ overhang blunt
What is DnaA?
The initiator protein for DNA replication in E. Coli
What is DNA Gyrase?
A topoisomerase which binds to chromosome ahead of replication for and relieves tension
Differentiate the two types of topoisomerase.
TPI I: Relax negative supercoils in E. Coli; Pos/neg in other types of prok; No ATP Use; Create Nick III DNA and reseal
TPI II: Create transient breaks in both strands; Requires ATP; Introduce Net supercoils to relieve pos supercoils; Can fix neg and pos supercoils
What is Quinoline?
- Antibiotic against gram-negative bacteria with minor gram positive activity
- Inhibits subunit of DNA gyrase and TPI IV in bacteria
What is DnaG?
Primase- synthesizes short strands of RNA
What is the primosome?
The prepriming complex of proteins on the Okazaki fragments and Primase enzyme
What is the role of DNA Ligasee?
- Join Okazaki fragments
- Joins DP I strand to DP III strand
What are the two main differences in Eukaryotic and prokaryotic DNA replication?
- # ORCs (Euk have multiple sites vs 1)
2. # DNA polymerases (Bacteria have 5; Euk can have to to 13 different ones)
What is the function of Telomerase?
Maintains length of Telomere in Euls
What causes histones to be positive as physiological pH?
High amounts of Lysine and Arginine
What is DNA Polymerase y?
- Replicative polymerase in mitochondrial DNA
What is most significant about Polymerase y?
It contains a 3’-5’ exonuclease domain which acts to proofread newly synthesized DNA strand
Which enzymes initiates mtDNA termination?
DNA Ligase III
What does the strand displacement model say?
MtDNA Replication is initiated at Theo distinct locations; OH and OL
What make sup the non coding region of mtDNA?
HSP - Heavy strand promoter
LSP - Light strand promoter
3 conserved sequence boxes
H-strand OR
TAS - Termination associated sequence
Where is the primer for Pol-y to begin synthesis at OH?
LSP
What does OL do in mtDNA synthesis?
Forms a stem-loop
What is the role of POLRMT in mtDNA synthesis?
Initiates primer synthesis from single stranded loop region
Why is MtDNA more likely to mutate?
- Reactive Oxidation f/ OXPHOS
- No DNA repair mechanism
Describe pathology of MERRF.
Myoclonic eplepsy and ragged red fiber disease
- Lack of muscular coordination (Myoclonus)
- Secondary features: Dementia, peptic atrophy, deafness, lipomata
- Ragged red fibers in skeletal muscle
- History in maternal transmission
Describe pathology of LHON
- Fast, sudden, painless loss of vision in both eyes in late teens
- LHON exhibit reduced penetrance; MEn have 40% and women have 10% chance of developing symptoms if they have mutation
