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DNA Replication

Replication is a polymerization reaction and
can be divided into stages of

initiation,

elongation and

termination.
….. complicated process

A supply of energy is required to unwind the helix

The single strands resulting from the unwinding tend to
form intrastrand base pairs

A single enzyme can catalyze only a limited number of physical and
chemical reactions and many reactions are needed in replication.

Several safeguards have evolved that are designed both to prevent
replication errors and to eliminate the rare errors that do occur.

Both circularity and the enormous size of the DNA molecules impose
geometric constraints on the replicative system and
how this fit into the system has to be understood.
Models for the replication of DNA
Meselson- Stahl Experiment
Semidiscontinuous replication
…..this model has a paradox,



• cellular DNA replication is semi conservative

• both daughter strands are extended simultaneously

• the strands of the parental duplex are antiparallel

• DNA polymerases extend DNA only in the 5’ → 3’ direction.
Mechanism of DNA replication

 Initiation
Elongation




                             Polymerase
 Poly (nucleotide)n-3’-OH + dNTP ⇔ Poly (nucleotide)n+1-3’-OH + PPi
Termination



In a unidirectionally replicating molecule, replication terminates at the origin.

In bidirectionally replicating molecule, it may be of two types:

5.   there might be definite termination sequence.

7. two growing points collide and termination occurs where ever the
    collision point happens to be.
Fidelity of DNA replication



 Transition mutations

   exchange of one purine, or pyrimidine, for another purine, or pyrimidine



Transversion mutations


  exchange of a purine for a pyrimidine or visa versa.
1. Light-dependent repair




               DNA photolyase


      uses light energy to cleave the covalent cross-link
2. Excision repair




                          Nucleotide excision repair
   Base excision repair
Nucleotide excision repair
Mismatch repair
Post-replication repair




                          Error prone repair system

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DNA replication

  • 1. DNA Replication Replication is a polymerization reaction and can be divided into stages of initiation, elongation and termination.
  • 2. ….. complicated process A supply of energy is required to unwind the helix The single strands resulting from the unwinding tend to form intrastrand base pairs A single enzyme can catalyze only a limited number of physical and chemical reactions and many reactions are needed in replication. Several safeguards have evolved that are designed both to prevent replication errors and to eliminate the rare errors that do occur. Both circularity and the enormous size of the DNA molecules impose geometric constraints on the replicative system and how this fit into the system has to be understood.
  • 3. Models for the replication of DNA
  • 6. …..this model has a paradox, • cellular DNA replication is semi conservative • both daughter strands are extended simultaneously • the strands of the parental duplex are antiparallel • DNA polymerases extend DNA only in the 5’ → 3’ direction.
  • 7.
  • 8. Mechanism of DNA replication Initiation
  • 9. Elongation Polymerase Poly (nucleotide)n-3’-OH + dNTP ⇔ Poly (nucleotide)n+1-3’-OH + PPi
  • 10. Termination In a unidirectionally replicating molecule, replication terminates at the origin. In bidirectionally replicating molecule, it may be of two types: 5. there might be definite termination sequence. 7. two growing points collide and termination occurs where ever the collision point happens to be.
  • 11. Fidelity of DNA replication Transition mutations exchange of one purine, or pyrimidine, for another purine, or pyrimidine Transversion mutations exchange of a purine for a pyrimidine or visa versa.
  • 12. 1. Light-dependent repair DNA photolyase uses light energy to cleave the covalent cross-link
  • 13. 2. Excision repair Nucleotide excision repair Base excision repair
  • 16. Post-replication repair Error prone repair system