The below mentioned article provides a short note on DNA repair synthesis.
Several types of damages, such as breakage in DNA strand, alteration of base pairs, cross linking of DNA with DNA or cross linking of DNA with proteins and pyrimidine dimer formation etc., may occur in chromosomes. These damages may be caused by mutagens produced within the cell itself (e.g., base changes due to tautomeric shift) or they may be caused by radiations (solar or artificial) and chemicals.
DNA damage may often interfere with the normal functioning of DNA during transcription and replication, which may lead to the death of the organism. In view of this, organisms have developed repair systems for damaged DNA. Some of the repair mechanisms are well studied, e.g., photo-reactivation, excision repair and recombinational repair; these are briefly described below.
Photo-Reactivation:
Ultraviolet (UV) light produces thymine dimers by inducing bond formation between two adjacent thymine bases on the same DNA strand (Fig. 3.18; 3.19). This leads to physical distortion of DNA double helix. Photo-reactivation process utilizes blue light of the visible spectrum.
A specific repair enzyme, “photolyase” recognizes dimer and binds to it. The enzyme when activated by the blue light (310-400 nm wave length), splits the thymine dimer (4-4 and 5-5 bonds formation).
This restores the two thymine residues into their original state and reestablishes the normal pairing between the complementary strands of the double helix (Fig. 3.19). As a result, the survival of UV-irradiated cells increases when they are exposed to visible light.
This system of DNA repair has been observed in several organisms, such as, algae, fungi, birds, frogs, bacteria and bacteriophages. However, mammals lack this system of DNA repair.
Excision repair system:
This repair system does not require light and can operate in dark. An endonuclease recognizes the thymine dimer present in a DNA strand and induces a nick near the dimer. The 3′-phosphate group is removed by the enzyme phosphatase (or 3′ exonuclease) to yield a free 3′-OH group.
Now the 5′ exonuclease removes the thymine dimer along with 6-7 nucleotides on either side of the dimer. In bacteria, the exonuclease function is performed by DNA polymerase I (Kornberg’s enzyme). The gap in strand created by the excision is then filled by DNA polymerase using the intact strand as template the nick remaining at the end is joined by polynucleotide ligase (Fig. 3.19).
A separate system of excision repair is found in some organisms such as, Micrococcus luteus and T4-infected E. coli. A specific enzyme “glycosylase” breaks the glycosylic bond (the C-N bond between pentose and nitrogenous bases) between thymine residue of the dimer and its deoxyribose sugar.
Thus the chain becomes devoid of a base; such a site is called “apyrimidine” or “apurine” (AP) site. The AP site is then cut by “AP endonuclease” and the excision repair process repairs the DNA.