Format

Send to

Choose Destination
ScientificWorldJournal. 2002 Feb 1;2:275-81.

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

Author information

1
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.

Abstract

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.

PMID:
12806015
PMCID:
PMC6009725
DOI:
10.1100/tsw.2002.99
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Hindawi Limited Icon for PubMed Central
Loading ...
Support Center