Chapter9 The Mutability and Repair of DNA

1
Chapter9 The Mutability and Repair of DNA

• Life and biodiversity depend on a happy balance
  between mutation and its repair

2
OUTLINE

• Replication errors and their repair
• DNA damage
• Repair of DNA damage

3
REPLICATION ERRORS AND THEIR REPAIR

• The nature of mutations
• The simplest mutation are switches of one base
  for another transitions and transversions
• Insertions or deletion of a nucleotide or a small
  number of nucleotides
• Extensive insertions and deletions and gross
  rearrangements of chromosome structure
• The overall rate of spontaneous mutations ranges
  from about 10_6 to 10_11 (hotspots)
• DNA microsatellites

4
REPLICATION ERRORS AND THEIR REPAIR

• Some replication errors escape proofreading

5
(No Transcript)
6
REPLICATION ERRORS AND THEIR REPAIR

• Mismatch repair removes errors that escape
  proofreading
• How is the DNA mended rapidly enough to prevent
  errors from becoming set in the genetic material
  as mutations?
• How does the cell distinguish the parental strand
  from the daughter strand?

7
REPLICATION ERRORS AND THEIR REPAIR

• In E.coli, mismatches are detected by a dimer of
  the mismatch repair protein MutS

8
(No Transcript)
9
REPLICATION ERRORS AND THEIR REPAIR

• 9-3

10
REPLICATION ERRORS AND THEIR REPAIR

• 9-5

11
REPLICATION ERRORS AND THEIR REPAIR

• Eukaryotic cells lack MutH and trick of using
  hemimethylation, and how does the mismatch repair
  system know which of the two strands to correct?
• Lagging strand Okazaki fragments Nick

12
DNA DAMAGE

• DNA undergoes damage spontaneously from
  hydrolysis and deamination

13
(No Transcript)
14
DNA DAMAGE

• DNA is damaged by Alkylation, Oxidation, and
  Radiation
• 9-8 9-9

15
DNA DAMAGE

• Mutations are also caused by base analogs and
  intercalating agents
• 9-10

16
(No Transcript)
17
REPAIR OF DNA DAMAGE

• Direct reversal of DNA damage
• Photoreactivation
• 9-11

18
REPAIR OF DNA DAMAGE

• The removal of the methyl group
• 9-12

19
REPAIR OF DNA DAMAGE

• Base excision repair enzymes remove damaged bases
  by a base-flipping mechanism
• 9-13

20
(No Transcript)
21
REPAIR OF DNA DAMAGE

• 9-14

22
REPAIR OF DNA DAMAGE

• Nucleotide excision repair enzymes cleave damaged
  DNA on either side of the lesion
• 9-16

23
(No Transcript)
24
REPAIR OF DNA DAMAGE

• Not only is nucleotide excision repair capable of
  mending damage throughout the genome, but it is
  also capable of rescuing RNA polymerase
• Transcription-coupled repair

25
REPAIR OF DNA DAMAGE

• 9-17

26
REPAIR OF DNA DAMAGE

• Recombination repairs DNA breaks by retrieving
  sequence information from undamaged DNA
• Chapter 10

27
REPAIR OF DNA DAMAGE

• Translesion DNA synthesis enables replication to
  proceed across DNA damage
• Highly errorprone
• SOS responnse

28
REPAIR OF DNA DAMAGE

• 9-18