It content details of DNA Damage, DNA Repair Mechanisms, DNA recombition

2.  DNA repair is a collection of processes by
which a cell identifies and corrects damage
to the DNA molecules that encode its
genome.
 A failure to repair damaged DNA produces :
mutation

3. a permanent (heritable) change in the
DNA sequence
 Substitution, deletion, or insertion of a base
pair.
 Chromosomal deletion, insertion, or
rearrangement.
Somatic mutations occur in somatic cells and
only affect the individual in which the
mutation arises.
Germ-line mutations alter gametes and passed
to the next generation.

4. DNA Lesions are sites of damage in the base-
pairing or structure of DNA.
They are classified as follows:
 Abasic Site: This is where a base is missing
from the DNA (note that the sugar-phosphate
backbone is still intact, just the base is
missing).
 Mismatch: These are caused by replication
errors, such as tautomerization, or the
spontaneous deamination of cytosine to uracil.

5.  Modified Bases: These lesions are caused by
changes to the bases themselves, such as the
methylation of guanine to O6MeG, which base-
pairs with thymine, or the UV-induced creation
of thymine dimers.
 Single-stranded breaks (SSB): This lesion is a
nick in the sugar-phosphate backbone of one
strand. This is caused by peroxides, Cu++ion,
oxygen radicals, or ionizing radiation.

6.  Double-stranded breaks (DSB): The most
lethal sort of lesion, this is where both
strand backbones are broken. This is
typically caused by ionizing radiation.
 Inter strand Crosslinks: This is where there
is an actual covalent linkage between the
two strands. DNA replication cannot proceed
past this point because helicase can’t melt
apart the base-pairs for polymerase. This is
caused by chemicals such as mitomycin C,
cisplatins, and psoralens.

7. hydrolatic
attack
oxidative
damage
uncontrolled
methylation
DNA frequently suffers from spontaneous alterations and chemical damage

8. G A CT
ds DNA Break Mismatch
Thymidine dimer
AP site
Covalent X-linking
ss Break
C-U deamination

10. Replication is highly accurate, but not perfect
Molecular Biology of the Gene, 5th Edition

11. Eukaryotes
MISMATCH REPAIR corrects replication errors

12. Some replication errors still escape detection: MUTATION
Molecular Biology of the Gene, 5th Edition
MUTATION
REPLICATION ERROR
(still can be repaired)
(a permanent change;
can not be repaired)

13. If all DNA damage were left
unrepaired, cells would quickly die
due to the accumulation of lethal
mutations and the inhibition of
essential processes relying on the
integrity of DNA (i.e. replication and
transcription)

14. If uncorrected, these changes may result in mutations

15. DNA repair is a collection of
processes by which a cell identifies
and corrects damage to
the DNA molecules that encode its
genome.

17. DIRECT REVERSAL
BASE EXCESSION REPAIR
NUCLEOTIDE EXCISION REPAIR
RECOMBITIONAL REPAIR
TRANSLESION DNA SYNTHESIS

18. a. Photoreactivation
b. Methyltransferase

21. DIRECT REVERSAL
BASE EXCESSION REPAIR
NUCLEOTIDE EXCISION REPAIR
RECOMBITIONAL REPAIR
TRANSLESION DNA SYNTHESIS

22. Base Excision Repair and Nucleotide Excision Repair
are the two major pathways for repairing DNA damage

23. DIRECT REVERSAL
BASE EXCESSION REPAIR
NUCLEOTIDE EXCISION REPAIR
RECOMBITIONAL REPAIR
TRANSLESION DNA SYNTHESIS

24. DNA damages are repaired by a recombination
mechanism known as sister-strand exchange.
 Homologous (or general)
between two homologous DNA sequences
 Site-Specific
between two defined DNA sequence elements
 Transposition
between specific DNA element and any DNA site
(we will go in details at the end of this slides)

25. DIRECT REVERSAL
BASE EXCESSION REPAIR
NUCLEOTIDE EXCISION REPAIR
RECOMBITIONAL REPAIR
TRANSLESION DNA SYNTHESIS

26. Error-prone repair
Occurs when the other repairs are
not efficient enough
Translesion synthesis is catalyzed by
a specialized class of DNA
polymerases, translesion
polymerases, that synthesize DNA
directly across the damage site.

27. Translesion DNA
synthesis
Catlyzed by a
specialized class of
DNA polymerases that
synthesize DNA
directily across the
site of the damage

28. The enzyme is not ‘reading’
sequence information from
the template
Translesion synthesis is often
highly error-prone

29. DNA damages are repaired by a
recombination mechanism known as sister-
strand exchange.
 Homologous (or general)
between two homologous DNA sequences
 Site-Specific
between two defined DNA sequence elements
 Transposition
between specific DNA element and any DNA
site

30. Homologous (or general)
between two homologous DNA sequences
 Site-Specific
between two defined DNA sequence elements
 Transposition
between specific DNA element and any DNA
site

31.  Homologous recombination is a type of genetic
recombination in which nucleotide sequences
are exchanged between two similar or identical
molecules of DNA.
 It is most widely used by cells to
accurately repair harmful breaks that occur on
both strands of DNA, known as double-strand
breaks.
 Homologous recombination also produces new
combinations of DNA sequences during meiosis.
 Homologous recombination is also used
in horizontal gene transfer to exchange genetic
material between different strains and species of
bacteria and viruses

32. Two distinct mechanisms repair double-strand breaks

33. Homologous recombination repairs strand breaks

34. Homologous recombination is crucial for meiosis
IZOMERIZATION OF A HOLLIDAY JUNCTION

44.  Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
 Transposition
between specific DNA element and any DNA
site

45. Lysogenic cycle involves integration of phage into the host chromosome by
SITE-SPECIFIC RECOMBINATION
Molecular Biology of the Gene, 5th Edition

46. The insertion of bacteriophage l genome into the host DNA
(recombination sites)
(recombinase)

47. Types of site-specific recombination
Molecular Biology of the Gene, 5th Edition
the darker red and blue boxes – the recombinase recognition sequences
the black arrows – the crossover regionsrecombination sites

48.  Homologous (or general)
between two homologous DNA sequences
 Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA
site

49. Unlike elements moving by site-specific recombination, TRANSPOSONS can insert
into any DNA sequence
Molecular Biology of the Gene, 5th Edition
(transposon)

50. Molecular Biology of the Gene, 5th Edition
Transposons can move with or without duplication

52. Thank you!
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