Updated: 5/6/2017

DNA Replication

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Evidence
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Overview 
  • Function
    • replicate cell genome in a manner that is highly accurate
  • Process 
    • DNA melted to expose single strand to expose origin of replication
    • single stranded binding proteins (SSBs) bind and stabilize melted DNA
    • RNA primer added in 5' → 3' direction by primase
    • DNA polymerase adds adds nucleotides in a 5' → 3'
      • DNA polymerase III in prokaryotes
      • DNA polymerase α and δ in eukaryotes
      • can edit mistakes with a 3' → 5' exonuclease activity
      • adds continuously on the leading strand
      • adds discontinuous Okazaki fragments on the lagging strand because it must synthesize in a 5' → 3' direction
    • DNA gyrase (topoisomerase II) breaks the DNA to prevent coiling
    • RNA primer removed
      • by RNAase H in eukaryotes and filled by a DNA polymerase
      • by DNA polymerase I in prokaryotes and can fill simultaneously
    • DNA ligase seals the nick between fragments
  • Differences between prokaryotes eukaryotes
    • prokaryotes
      • single origin of replication
    • eukaryotes
      • multiple origins of replication
  • Clinical importance
    • antibiotics
      • quinolones, fluoroquinolones block bacterial topoisomerase
        • used to treat aerobic gram negatives in UTIs and gonorrhea
        • e.g. drugs ending in -floxacin
    • cancer chemotherapy
      • etoposide, teniposide block eukaryotic topoisomerase
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.BC.4707) A 55-year-old male with a 60 pack-year smoking history presents to his oncologist for ongoing management of his recently diagnosed small cell lung cancer. His oncologist discusses several options and decides to start the chemotherapeutic medication, etoposide. The patient is warned that one side effect of this drug is myelosuppression so he should be vigilant for development of any infectious symptoms. The beneficial effect of this drug in treating cancer is most likely due to which of the following effects? Review Topic

QID: 108444
1

Alkylation of DNA

18%

(42/234)

2

Crosslinking of DNA

14%

(32/234)

3

DNA intercalation

13%

(31/234)

4

Inhibition of supercoil relaxation

40%

(93/234)

5

Stabilization of microtubules

11%

(26/234)

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(M1.BC.73) A mutant stem cell was created by using an inducible RNAi system, such that when doxycycline is added, the siRNA targeting DNA helicase is expressed, effectively knocking down the gene for DNA helicase. Which of the following will occur during DNA replication? Review Topic

QID: 106556
1

DNA is not unwound

73%

(157/215)

2

DNA supercoiling is not relieved

13%

(29/215)

3

The two melted DNA strands reanneal

5%

(11/215)

4

The RNA primer is not created

2%

(4/215)

5

Newly synthesized DNA fragments are not ligated

5%

(11/215)

M1

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(M1.BC.11) Although nucleotide addition during DNA replication in prokaryotes proceeds approximately 20-times faster than in eukaryotes, why can much larger amounts of DNA be replicated in eukaryotes in a time-effective manner? Review Topic

QID: 100076
1

Eukaryotes have less genetic material to transcribe

0%

(0/25)

2

Eukaryotes have fewer polymerase types

4%

(1/25)

3

Eukaryotes have helicase which can more easily unwind DNA strands

8%

(2/25)

4

Eukaryotes have multiple origins of replication

88%

(22/25)

5

Eukaryotes do not have exons

0%

(0/25)

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