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MOLECULAR
Section I - DNA Replication
E. Histone methylation → ↓ DNA transcription
I. DNA structure (Figure 2.1.1)
F. Histone acetylation → ↑ DNA transcription
A. DNA is complementary to the opposite strand
(cytosine pairs with guanine and thymine pairs
II. DNA replication (Figure 2.1.2)
with adenine).
A. Helicase separates the DNA at the replication
B. DNA wrapped around eight histones is called a
fork.
nucleosome.
B. Single-stranded binding proteins bind to
C. The first histone (H1) is responsible for linking
the DNA and prevent the two strands from
nucleosomes together.
reannealing.
D. Nucleosomes tightly packed together results in
C. The region where DNA replication begins is
the formation of a chromosome.
called the origin of replication.
1. Tightly packed → heterochromatin (not
D. Primase anneals to the 3’ end of the DNA and
accessible to transcription proteins)
synthesizes a primer.
2. Loosely packed → euchromatin
(transcriptionally active)

Figure 2.1.1 - DNA structure


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E. DNA polymerase III binds to the primer and 2. Eukaryotic (topoisomerase I & II)
adds deoxynucleotides onto the 3’ end of the a) Irinotecan
primer (eukaryotes perform this function via
b) Topotecan
DNA polymerase epsilon).
c) Etoposide
1. Synthesizes DNA in the 5’ → 3’ direction.
d) Teniposide
2. 3’ → 5’ exonuclease activity.
K. DNA polymerase I vs DNA polymerase III
F. The DNA strand being synthesized towards the
replication fork is called the leading strand. 1. DNA polymerase I (“DNA polymerase I only
goes in one direction”)
1. Synthesized continuously
a) 5’ → 3’ synthesis (“contrive at five”)
G. The DNA strand being synthesized away from
the replication fork is called the lagging strand. b) 5’ → 3’ exonuclease
L. DNA polymerase III
1. Synthesized discontinuously resulting in the
formation of Okazaki fragments. 1. 5’ → 3’ synthesis
H. DNA polymerase I (eukaryotes perform removal 2. 3’ → 5’ exonuclease
of primers via DNA polymerase delta) removes M. Telomerase
the RNA primers and replaces them with DNA.
1. Telomere: region at the end of a
1. Synthesizes DNA in the 5’ → 3’ direction. chromosome
2. 5’ → 3’ exonuclease activity. 2. Telomerase: enzyme that adds DNA to the
I. DNA ligase joins the Okazaki fragments 3’ end of chromosomes to prevent the loss
of genetic material with every duplication.
J. Topoisomerases remove supercoils in DNA.
1. Prokaryotic (topoisomerase II & IV)
a) Fluoroquinolones

Figure 2.1.2 - DNA replication


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REVIEW QUESTIONS ?
3. A 76-year-old male is admitted to the hospital
1. A new experimental drug is found to inhibit for community acquired pneumonia. A sputum
histone deacetylase. How will this drug most culture is obtained in hopes of isolating the
likely alter transcription? pathogen and determining antibiotic sensitivity.
• Acetylation of histones → ↑ transcription As the organism grows, its DNA is extracted and
• Deacetylation of histones → ↓ transcription analyzed. Detailed analysis of fragments from
• Deacetylase is an enzyme that removes partially replicated DNA reveals the presence
acetyl groups on histones of ribose sugar molecules with an increased
• The drug described inhibits deacetylase number of hydroxyl modifications. These
→ ↑ number of acetylated histones → ↑ fragments are most likely degraded by what
transcription enzyme during DNA replication?

• “Detailed analysis of fragments from par-


tially replicated DNA reveals the presence
of ribose sugar molecules with an increased
number of hydroxyl modifications.” →
referencing RNA (ribose contains one more
hydroxyl group than deoxyribose)
• During DNA replication RNA is present in
the form of primers
• RNA primers are degraded by the enzyme
2. A pathologist is studying DNA from staph aureus DNA polymerase I
wound infections. She isolates an enzyme and
studies its activity during DNA replication. She
finds that this particular enzyme possesses 5’ to
3’ exonuclease activity. What enzyme has she
most likely isolated?

• DNA polymerase I has 5’ to 3’ exonuclease


activity

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