Nucleic Acids Research Advance Access originally published online on April 16, 2007
Nucleic Acids Research 2007 35(9):2924-2935; doi:10.1093/nar/gkm126
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Nucleic Acids Research, 2007, Vol. 35, No. 9 2924-2935
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
Loop II of DNA polymerase beta is important for polymerization activity and fidelity
1Department of Therapeutic Radiology and Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA and 2Center for Medical Sciences, Wadsworth Center, Albany, New York 12201, USA
*To whom correspondence should be addressed. Tel: 203-737-2626; Fax: 203-785-6309; Email: joann.sweasy{at}yale.edu
Received January 15, 2007. Revised February 14, 2007. Accepted February 14, 2007.
The accurate replication and transmission of genetic information is critical in the life of an organism. During its entire lifespan, the genetic information is constantly under attack from endogenous and exogenous sources of damage. To ensure that the content of its genetic information is faithfully preserved for synthesis and transmission, eukaryotic cells have developed a complex system of genomic quality control. Key players in this process are DNA polymerases, the enzymes responsible for synthesizing the DNA, because errors introduced into the genome by polymerase can result in mutations. We use DNA polymerase beta (pol ß) as a model system to investigate mechanisms of preserving fidelity during nucleotide incorporation. In the study described here, we characterized the role that loop II of pol ß plays in maintaining the activity and fidelity of pol ß. We report here that the absence or shortening of loop II compromises the catalytic activity of pol ß. Our data also show that loop variants of a specific length have a lower fidelity when compared to the wild-type polymerase. Taken together, our results indicate that loop II is important for the catalytic activity and fidelity of pol ß.