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DNA Replication Professor M. J. Chorney MAGNET School for Medicine and Public Health, September 30, 2013

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Page 1: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

DNA Replication

Professor M. J. Chorney

MAGNET School for Medicine and

Public Health, September 30, 2013

Page 2: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 4-3 Molecular Biology of the Cell (© Garland Science 2008)

Review

Page 3: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 4-4 Molecular Biology of the Cell (© Garland Science 2008)

Review

Page 4: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 4-5 Molecular Biology of the Cell (© Garland Science 2008)

Review

Page 5: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-2 Molecular Biology of the Cell (© Garland Science 2008)

DNA serves as a template for its own synthesis-semiconservative

replication

Page 6: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-5 Molecular Biology of the Cell (© Garland Science 2008)

Page 7: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-3 Molecular Biology of the Cell (© Garland Science 2008)

The all important

site for extension

Page 8: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-4 Molecular Biology of the Cell (© Garland Science 2008)

DNA Polymerase Simulation and Model

Page 9: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008)

The pol has exonuclease activity which we previously talked

About, involved in mismatch repair, called more specifically

Proofreading/Editing

Page 10: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Table 5-1 Molecular Biology of the Cell (© Garland Science 2008)

Page 11: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-7 Molecular Biology of the Cell (© Garland Science 2008)

DNA polymerase requires a PRIMER WHICH IS MADE

FROM RNA BY RNA PRIMASE!!! BOTH STRANDS

THE PRIMERS ARE EVENTUALLY REMOVED

Page 12: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-12 Molecular Biology of the Cell (© Garland Science 2008)

Page 13: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-11 Molecular Biology of the Cell (© Garland Science 2008)

No

primer

required

for RNA primase

Page 14: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-10 Molecular Biology of the Cell (© Garland Science 2008)

For Advanced

Consideration

Why doesn’t

DNA extend

from the 5’

end?

It has to do

with phosphates

and proofreading

Page 15: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-19a Molecular Biology of the Cell (© Garland Science 2008)

Page 16: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-19b,c Molecular Biology of the Cell (© Garland Science 2008)

Page 17: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-25 Molecular Biology of the Cell (© Garland Science 2008)

Page 18: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-44 Molecular Biology of the Cell (© Garland Science 2008)

Review Green arrow, methylation sites

Blue arrow, hydrolytic cleavage

Red arrow, oxidation

Page 19: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-45 Molecular Biology of the Cell (© Garland Science 2008)

Two examples, review

Page 20: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-46 Molecular Biology of the Cell (© Garland Science 2008)

Thymine

dimers

Page 21: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-47 Molecular Biology of the Cell (© Garland Science 2008)

Changes can give rise to mutations

Page 22: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-48 Molecular Biology of the Cell (© Garland Science 2008)

Page 23: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-49 Molecular Biology of the Cell (© Garland Science 2008)

The glycosylase would cleave out the base

Note the helix

distortion

Page 24: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Figure 5-50a Molecular Biology of the Cell (© Garland Science 2008)

Thymine has no amino group

Page 25: Molecular Biology of the Cell - Susquehanna …...Figure 5-9 Molecular Biology of the Cell (© Garland Science 2008) The pol has exonuclease activity which we previously talked About,

Explain:

1.5’-3’ and its relevance to strand synthesis

2.RNA primase activity

3.Okazaki fragments

4.Proofreading

5.Helicase

6.Leading versus lagging strand synthesis

7.Semiconservative replication of dna

8.The replication fork, replication bubble