Novel inhibition of archaeal family-D DNA polymerase by uracil

Tomas T. Richardson, Louise Gilroy, Yoshizumi Ishino, Bernard A. Connolly, Ghislaine Henneke

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 singlestranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability.

Original languageEnglish
Pages (from-to)4207-4218
Number of pages12
JournalNucleic acids research
Volume41
Issue number7
DOIs
Publication statusPublished - Apr 1 2013

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Uracil
DNA-Directed DNA Polymerase
Polymerization
DNA
Exonucleases
Reading
Enzymes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Richardson, T. T., Gilroy, L., Ishino, Y., Connolly, B. A., & Henneke, G. (2013). Novel inhibition of archaeal family-D DNA polymerase by uracil. Nucleic acids research, 41(7), 4207-4218. https://doi.org/10.1093/nar/gkt083

Novel inhibition of archaeal family-D DNA polymerase by uracil. / Richardson, Tomas T.; Gilroy, Louise; Ishino, Yoshizumi; Connolly, Bernard A.; Henneke, Ghislaine.

In: Nucleic acids research, Vol. 41, No. 7, 01.04.2013, p. 4207-4218.

Research output: Contribution to journalArticle

Richardson, TT, Gilroy, L, Ishino, Y, Connolly, BA & Henneke, G 2013, 'Novel inhibition of archaeal family-D DNA polymerase by uracil', Nucleic acids research, vol. 41, no. 7, pp. 4207-4218. https://doi.org/10.1093/nar/gkt083
Richardson, Tomas T. ; Gilroy, Louise ; Ishino, Yoshizumi ; Connolly, Bernard A. ; Henneke, Ghislaine. / Novel inhibition of archaeal family-D DNA polymerase by uracil. In: Nucleic acids research. 2013 ; Vol. 41, No. 7. pp. 4207-4218.
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