Biomaterial Database

The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy. 2002

Igor V Shevelev, and Kristijan Ramadan, and Ulrich Hübscher

Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.

Proofreading function by the 3'-->5' exonuclease of DNA polymerase delta (pol delta) is consistent with the observation that delta efficiency of the associated exonuclease can lead to a strong mutation phenotype, high error rates during DNA replication, and ultimately cancer. We have isolated pol delta from isotonic (pol delta(i)) and detergent (pol delta(d)) calf thymus extracts. Pol delta had a 20-fold higher ratio of exonuclease to DNA polymerase than pol deltai. This was due to the physical association of the TREX2 3'-->5' exonuclease to pol delta(d), which was missing from pol delta(i). Pol delta(d) was fivefold more accurate than pol i under error-prone conditions (1 mM dGTP and 20 dATP, dCTP, and dTTP) in a M13mp2 DNA forward mutation assay, and fourfold more accurate than pol delta(i) under error-prone conditions (1 mM dGTP and 20 microM dATP, dCTP, and dTTP) in a M13mp2 DNA forward mutation assay, and fourfold more accurate in an M13mp2T90 reversion assay. Under error-free conditions (20 microM each of the four dNTPs), however, both polymerases showed equal fidelity. Our data suggested that autonomous 3' --> 5' exonucleases, such as TREX2, through its association with pol delta can guarantee high fidelity under difficult conditions in the cell (e.g., imbalance of dNTPs) and can add to the accuracy of the DNA replication machinery, thus preventing mutagenesis.

UI	MeSH Term	Description	Entries
D010750	Phosphoproteins		Phosphoprotein
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004258	DNA Polymerase III	A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II.	DNA Polymerase delta,DNA-Dependent DNA Polymerase III,DNA Pol III,DNA Dependent DNA Polymerase III,Polymerase III, DNA,Polymerase delta, DNA
D005090	Exodeoxyribonucleases	A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.	DNA Exonucleases,Exonucleases, DNA
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013950	Thymus Gland	A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.	Thymus,Gland, Thymus,Glands, Thymus,Thymus Glands
D016296	Mutagenesis	Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.	Mutageneses
D025941	Protein Interaction Mapping	Methods for determining interaction between PROTEINS.	Interaction Mapping, Protein,Interaction Mappings, Protein,Mapping, Protein Interaction,Mappings, Protein Interaction,Protein Interaction Mappings