1 of 36

DNA Repair + Telomeres

2 of 36

Replication In Proks Vs Euks

1000 nucleotides per second

100 nucleotides per second

3 of 36

Replication In Proks Vs Euks

4 of 36

Replication In Proks Vs Euks

5 of 36

6 of 36

Proofreading

7 of 36

Proofreading

Incorrect alignment�3’ hydroxyl is misaligned and DNA pol cannot add more nucleotides

8 of 36

Proofreading

3’ 🡪 5’ exonuclease activity

5’ 🡪 3’ polymerase activity

9 of 36

Nucleotide Mismatches

  • Let’s investigate ideas about how errors occur��
  • Think-Pair-Share:�Why can’t two pyrimidines or two purines bind?

10 of 36

Nucleotide Mismatches

3D Shape!!!!!!

  • What could cause a purine to pair with the wrong pyrimidine?

11 of 36

Nucleotide Mismatches

Tautomeric shifts in nucleotide bases.

The purine and pyrimidine bases in DNA exist in two different tautomers, or chemical forms. ��(A) Nucleotide bases shift from their common “keto” form to their rarer, tautomeric “enol” form.

​

© 2014 Nature Education Adapted from Pierce, Benjamin. Genetics: A Conceptual Approach, 2nd ed. All rights reserved.

12 of 36

Nucleotide Mismatches

(B) In common base pair arrangements, thymine (T) binds adenine (A), and cytosine (C) binds with guanine (G).

(C) Rare base-pairing arrangements result when one nucleotide in a base pair is the rare form instead of the common form. There is little evidence that this is a common occurrence.

Tautomeric Shift

13 of 36

Nucleotide Mismatches

(D) A shift in the position of nucleotides causes a wobble between a normal thymine and normal guanine. An additional proton on adenine causes a wobble in an adenine-cytosine base-pair. �Evidence suggests this is more common.

(B) In common base pair arrangements, thymine (T) binds adenine (A), and cytosine (C) binds with guanine (G).

(d)

Wobble

14 of 36

Mismatch Repair

  • How often do mismatches occur?
    • ~ 1 per every 100,000 nucleotides
      • If humans have 6 billion bases to copy = 120,000 errors

​

  • Proofreading may catch more than 99%
    • This still results in many mismatches
    • Cells therefore have “mismatch repair” mechanism that work on newly synthesized DNA

15 of 36

Mismatch Repair

16 of 36

17 of 36

Damage to DNA

18 of 36

Learn More

https://www.khanacademy.org/science/high-school-biology/hs-molecular-genetics/hs-discovery-and-structure-of-dna/a/dna-proofreading-and-repair

19 of 36

DNA Polymerase II

  • This enzyme is currently not well understood.�
  • Slower than DNA pol III
  • Possibly less error prone
  • Possibly recruited more often for repair

Pretty

20 of 36

Telomeres

21 of 36

Telomeres

5'-TTAGGG-3' in humans and other mammals.

22 of 36

Telomeres

23 of 36

Shortening Telomeres

24 of 36

Shortening Telomeres

25 of 36

Shortening Telomeres

26 of 36

Shortening Telomeres

27 of 36

Shortening Telomeres

  • Once the telomere is gone, this is usually a trigger for cells to stop replicating entirely
  • Sometimes this triggers apoptosis (controlled cell death)
  • Can you think of reasons why this process could be beneficial?

28 of 36

Telomeres

29 of 36

Telomeres Linked to Aging?

30 of 36

Telomeres Linked to Aging?

31 of 36

Telomerase

32 of 36

Telomerase

33 of 36

Telomerase

34 of 36

Telomerase

35 of 36

Telomerase

36 of 36

Homework

  • Read Chapters 14.4-14.5