Question

Describe the mechanism underlying the below repair mechanisms.

a. Mismatch Repair

b. Postreplication Repair

c. SOS Repair

d. Photoreactivation Repair

e. Base Excision Repair

f. Nucleotide Excision Repair

g. Doublestranded Break Repair

Answer 1

Mismatch repair - DNA polymerases are enzymes that synthesise new DNA. In the process, it can also check if it has incorporated the correct base into newly synthesized strand. If not, it can remove and reincorporate the correct base. This is called proofreading.

Most of the errors are corrected in proofreading. However, few slip through. In such cases, mismatch repair helps to correct small insertions or deletions that take place in new DNA strand.

Once a mismatch is recognised in DNA sequence, a group of proteins recognise it and bind to the site of mismatched bases. The portion of mismatched DNA and its neighbours are cut by proteins. DNA polymerase then synthesizes the missing section of DNA with newly synthesized bases. DNA ligase then seals the gaps in DNA backbone.

Postreplication repair - Sometimes, damage to the DNA can take place after the process of replication. This is the repair that is done to DNA that already underwent replication.

This process takes place downstream of the lesion, because replication is blocked at actual site of damage. Short segments of DNA, called okazaki fragments are synthesised. The gap left at damaged site is filled through recombination repair, that uses sequence from undamaged sister chromosome.

SOS repair - Save our soul repair. This is a state of global response to DNA damage.

Here, the system tries to repair the heavily damaged bases in DNA through base excision and replacement, and there wont be a template also to guide selection. As such, this is highly error prone and is the major cause of mutations. The cell will allow this as a last resort to fix the damaged DNA. In essence, genetic integrity is being sacrified for the survival of cells.

RecA is the major protein involved in this SOS reponse, and is specifically stimulated by the presence of single stranded DNA. It starts the repair process by inactivating the lexA protein.

Photoreactivation repair - Exposure of DNA to ultraviolet light can cause adjacent thymine residues to form thymine dimers. UV light is lethal to cellular DNA and this has to be repaired.

This repair mechanism removes the dimers by using energy obtained from visible light. DNA photolyases bind to the sites in DNA that contain these kinks because of dimers. Upon excitation by blue light, they change confirmation breaking the dimers in process.

Folate, is used to harvest light energy, and FADH is reduced to FADH2. The excited FADH2  will transfer high energy electron to dimer, casuing the structure to break apart.