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Papers In Press, published online ahead of print June 11, 2001
J. Biol. Chem, 10.1074/jbc.M102694200
Submitted on March 26, 2001
Revised on May 30, 2001
Accepted on June 11, 2001
promiscuous mismatch extension
NICHD, NIH, Bethesda, MD 20892-2725
Corresponding Author: woodgate{at}helix.nih.gov
Human DNA polymerase 
is a low fidelity template copier that preferentially catalyzes the incorporation of the wobble base G, rather than Watson-Crick base A, opposite template T (Tissier et al (2000) Genes Dev. 14, 1642-50; Johnson et al (2000) Nature. 406, 1015-9; Zhang et al (2000) Mol. Cell Biol. 20, 7099-108). Here, we report on its ability to extend all 12 possible mispairs and 4 correct pairs in different sequence contexts. Extension from both matched and mismatched primer termini is generally most efficient and accurate when A is the next template base. In contrast, extension occurs less efficiently and accurately when T is the target template base. A striking exception occurs during extension of a G:T mispair, where the enzyme switches specificity gpreferringh to make a correct A:T base pair immediately downstream from an originally favored G:T mispair. Pol generates a variety of single and tandem mispairs with high frequency implying that it may act as a strong mutator when copying undamaged DNA templates in vivo. Even so, its limited ability to catalyze extension from a relatively stable primer/template containing a gburiedh mismatch suggests that pol -catalyzed errors are confined to short template regions.
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