DNA-polymerase: mechanisms of replication fidelity

Poljak, Kristina (2009) DNA-polymerase: mechanisms of replication fidelity. Bachelor's thesis, Faculty of Science > Department of Biology.

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DNA-polymerases are complex, multidomain enzymes that catalyze reactions of DNA replication. They achieve rates of synthesis that support physiological growth rates and yet preserve relatively high fidelity. The goal of this seminar was to explain how do they manage to do that. It has been shown that they achieve that by using distinct domains for polymerization and for proofreading, with antagonistic catalytic functions. We can draw general conclusion that high fidelity synthesis of DNA are driven by several factors: complementary base pairing, induced fit and 3’-5’ exonuclease activity. Firsty, initial selection of correct base pair is achieved on the basis of geometry. Then, binding of the correct nucleotide induces conformational change, which provides steric check for the proper base pair geometry, followed by a rapid incorporation of nucleotide into the growing polymer. Mismatch inhibits this conformational change as well as polymerization, allowing the transfer of newly synthesized chain into editing site, where the incorrect base is removed by 3’-5’ exonuclease. The overall fidelity approaches one error in 1010 by a combination of selectivity in polymerization (105-106) and in proofreading (103-104). Also, beside the high fidelity polymerases there are low fidelity ones, which are not so specific, and are therefore suitable for the replication of damaged DNA molecules, which can not be carried out by normal DNA-polymerases. It is necessary to note that no DNA-polymerase works alone. DNA replication involves huge complexes of DNA-polymerases with multitude accessory proteins, which in many ways affect its processivity and efficiency. Since the complexity of polymerization reactions in vitro does not even approximate those in the cell, many research remains to be done that will give us a clearer and more detailed picture of how do cells replicate their own genome.

Item Type: Thesis (Bachelor's thesis)
Supervisor: Gruić Sovulj, Ita
Date: 2009
Number of Pages: 22
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 08 Dec 2014 11:42
Last Modified: 16 Feb 2016 13:57
URI: http://digre.pmf.unizg.hr/id/eprint/3482

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