DNA replication fidelity

Yang W, Shen C, Ji Q, An H, Wang J, Liu Q, Zhang Z (2009) Food storage material silver nanoparticles interfere with DNA replication fidelity and bind with DNA. Nanotechnology 20 085102... 

Wong, I., Patel, S. S., and Johnson, K. A. (1991). An induced-fit kinetic mechanism for DNA replication fidelity Direct measurement by single-turnover kinetics. Biochemistry 30, 526-537. 

Kunkel TA, Bebenek K. DNA replication fidelity. Annu. Rev. Bioehem. 2000 69 497-529. 

DNA replication yields two DNA molecules identical to die original one, ensuring transmission of genetic information to daughter cells widi exceptional fidelity. 

Past-active In some recent studies,... Cr + increased DNA polymerase processivity and decreased its fidelity during DNA replication in vitro (13-17). (Adapted from Plaper et ak, 2002)... 

A. In order that a complete complement of the genetic material may be inherited by daughter cells during cell division or by offspring from parents, the DNA must be copied with high fidelity by a process called DNA replication. 

D. DNA replication is regulated as a balance between high speed and efficiency (pro-cessivity) and the need for high fidelity. 

Despite the near-perfect fidelity of genetic replication, infrequent, unrepaired mistakes in the DNA replication process lead to changes in the nucleotide sequence of DNA, producing a genetic mutation (Fig. 1-32) and changing the instructions for some cellular component. Incorrectly repaired damage to one of the DNA strands has the same effect. Mutations in the DNA handed down... 

FIGURE 25-6 Contribution of base-pair geometry to the fidelity of DNA replication, (a) The standard A=T and G=C base pairs have very similar geometries, and an active site sized to fit one (blue shading) will generally accommodate the other, (b) The geometry of incorrectly paired bases can exclude them from the active site, as occurs on DNA polymerase I. 

Like bacteria, eukaryotes have several types of DNA polymerases. Some have been linked to particular functions, such as the replication of mitochondrial DNA. The replication of nuclear chromosomes involves DNA polymerase a, in association with DNA polymerase S. DNA polymerase a is typically a multisubunit enzyme with similar structure and properties in all eukaryotic cells. One subunit has a primase activity, and the largest subunit (Afr -180,000) contains the polymerization activity. However, this polymerase has no proofreading 3 —>5 exonuclease activity, making it unsuitable for high-fidelity DNA replication. DNA polymerase a is believed to function only in the synthesis of short primers (containing either RNA or DNA) for Okazaki fragments on the lagging strand. These primers... 

The fidelity of DNA replication is maintained by (1) base selection by the polymerase, (2) a 3 —>5 proofreading exonuclease activity that is part of most DNA polymerases, and (3) specific repair systems for mismatches left behind after replication. 

Excellent summary of the molecular basis of replication fidelity by a DNA polymerase—base-pair geometry as well as hydrogen bonding. 

TWn relatively recent developments have added to our knowledge significantly concerning how DNA replication occurs with fidelity or in what molecular biologists and biochemists call a processive polymerase activity. DNA polymerase is the enzyme which actually polymerizes (adds DNA precursors or building blocks) DNA. There are many such DNA polymerases in pro- and eukaryotic cells that have different functions but the main enzyme in prokaryotes is DNA polymerase 111 and in Eukaryotes. DNA polymerases alpha, delta, and epsilon. All four of these DNA polymerases are made of subunits. 

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