The fidelity of DNA replication determines the genome stability and it plays a main role in evolution of species. The DNA replication fidelity is a key factor of mutations which in turn leads to many human diseases. The high fidelity of DNA replication in E.coli is achieved by DNA polymerase III holoenzyme, which is a complex of 17 proteins. This is responsible for simultaneous replication of both leading and lagging DNA strand with high speed and high fidelity. There are also four other accessory DNA polymerases present in E.coli such as Pol I, II, IV and V. Pol II plays an important role in proofreading of DNA intra-strand crosslinks, DNA strand exposed to UV irradiation, oxidation, stress-induced mutagenesis. This enzyme is responsible for translesion synthesis. Pol IV and V are specific to lagging stand. Pol IV is responsible for proceeding the DNA replication even when there is a mismatch. The Pol IV has a high constitutive intracellular concentration. Pol V is induced constitutively in the absence of exogenous DNA damage. The primary role of Pol I in DNA replication is to remove RNA primers and fill the resulting gap during maturation of Okazaki fragments in the lagging strand. In eukaryotes, the replication of leading and lagging strands takes place by Pol and Pol respectively, which leads to fidelity differences. Whereas in E.coli the replication of both leading and lagging strands takes place by same enzyme polymerase III. This is also one of the reason why E.coli has high fidelity of DNA replication. The tau subunit of Pol III plays a central role in DNA replication fidelity, as it interacts with both leading and lagging strand. This subunit also contributes for polymerase switching during replication. Solution The fidelity of DNA replication determines the genome stability and it plays a main role in evolution of species. The DNA replication fidelity is a key factor of mutations which in turn leads to many human diseases. The high fidelity of DNA replication in E.coli is achieved by DNA polymerase III holoenzyme, which is a complex of 17 proteins. This is responsible for simultaneous replication of both leading and lagging DNA strand with high speed and high fidelity. There are also four other accessory DNA polymerases present in E.coli such as Pol I, II, IV and V. Pol II plays an important role in proofreading of DNA intra-strand crosslinks, DNA strand exposed to UV irradiation, oxidation, stress-induced mutagenesis. This enzyme is responsible for translesion synthesis. Pol IV and V are specific to lagging stand. Pol IV is responsible for proceeding the DNA replication even when there is a mismatch. The Pol IV has a high constitutive intracellular concentration. Pol V is induced constitutively in the absence of exogenous DNA damage. The primary role of Pol I in DNA replication is to remove RNA primers and fill the resulting gap during maturation of Okazaki fragments in the lagging strand. In eukaryotes, the replication of leading .