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Novel inhibition of archaeal family-D DNA polymerase by uracil

Lookup NU author(s): Dr Tom Richardson, Louise Gilroy, Professor Bernard Connolly

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Abstract

Archaeal family-D DNA polymerase is inhibited by the presence of uracil in DNA template strands. When the enzyme encounters uracil, following three parameters change: DNA binding increases roughly 2-fold, the rate of polymerization slows by a factor of ~5 and 3'–5' proof-reading exonuclease activity is stimulated by a factor of ~2. Together these changes result in a significant decrease in polymerization activity and a reduction in net DNA synthesis. Pol D appears to interact with template strand uracil irrespective of its distance ahead of the replication fork. Polymerization does not stop at a defined location relative to uracil, rather a general decrease in DNA synthesis is observed. ‘Trans’ inhibition, the slowing of Pol D by uracil on a DNA strand not being replicated is also observed. It is proposed that Pol D is able to interact with uracil by looping out the single- stranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability.

Publication metadata

Author(s): Richardson TT, Gilroy L, Ishino Y, Connolly BA, Heneneke G

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 2013

Volume: 41

Issue: 7

Pages: 4207-4218

Print publication date: 13/02/2013

Date deposited: 15/07/2013

ISSN (print): 0305-1048

ISSN (electronic): 1362-4962

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/nar/gkt083

DOI: 10.1093/nar/gkt083

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