Novel inhibition of archaeal family-D DNA polymerase by uracil
| Type | Article | ||||||||
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| Date | 2013-04 | ||||||||
| Language | English | ||||||||
| Author(s) | Richardson Tomas T.1, Gilroy Louise1, Ishino Yoshizumi2, Connolly Bernard A.1, Henneke Ghislaine 3, 4, 5 |
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| Affiliation(s) | 1 : Newcastle Univ, Inst Cell & Mol Biosci ICaMB, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. 2 : Kyushu Univ, Grad Sch Bioresourse & Bioenvironm Sci, Dept Biosci & Biotechnol, Fukuoka 8128581, Japan. 3 : IFREMER, Ctr Brest, UMR 6197, LM2E, F-29280 Plouzane, France. 4 : CNRS, LM2E, UMR 6197, F-29280 Plouzane, France. 5 : Univ Brest, UEB, LM2E, UMR 6197, F-29280 Plouzane, France. |
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| Source | Nucleic Acids Research (0305-1048) (Oxford Univ Press), 2013-04 , Vol. 41 , N. 7 , P. 4207-4218 | ||||||||
| DOI | 10.1093/nar/gkt083 | ||||||||
| WOS© Times Cited | 13 | ||||||||
| 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 similar to 5 and 3'-5' proof-reading exonuclease activity is stimulated by a factor of similar to 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. | ||||||||
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