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Intrinsic Apurinic/apyrimidinic (AP) Endonuclease Activity Enables Bacillus Subtilis DNA Polymerase X to Recognize, Incise, and Further Repair Abasic Sites

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Specialty Science
Date 2010 Oct 27
PMID 20974932
Citations 12
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Abstract

The N-glycosidic bond can be hydrolyzed spontaneously or by glycosylases during removal of damaged bases by the base excision repair pathway, leading to the formation of highly mutagenic apurinic/apyrimidinic (AP) sites. Organisms encode for evolutionarily conserved repair machinery, including specific AP endonucleases that cleave the DNA backbone 5' to the AP site to prime further DNA repair synthesis. We report on the DNA polymerase X from the bacterium Bacillus subtilis (PolX(Bs)) that, along with polymerization and 3'-5'-exonuclease activities, possesses an intrinsic AP-endonuclease activity. Both, AP-endonuclease and 3'-5'-exonuclease activities are genetically linked and governed by the same metal ligands located at the C-terminal polymerase and histidinol phosphatase domain of the polymerase. The different catalytic functions of PolX(Bs) enable it to perform recognition and incision at an AP site and further restoration (repair) of the original nucleotide in a standalone AP-endonuclease-independent way.

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References
1.
Kavli B, Sundheim O, Akbari M, Otterlei M, Nilsen H, Skorpen F . hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. J Biol Chem. 2002; 277(42):39926-36. DOI: 10.1074/jbc.M207107200. View

2.
Fromme J, Banerjee A, Verdine G . DNA glycosylase recognition and catalysis. Curr Opin Struct Biol. 2004; 14(1):43-9. DOI: 10.1016/j.sbi.2004.01.003. View

3.
Carthew R, Chodosh L, Sharp P . An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985; 43(2 Pt 1):439-48. DOI: 10.1016/0092-8674(85)90174-6. View

4.
Tabor S, Richardson C . A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci U S A. 1985; 82(4):1074-8. PMC: 397196. DOI: 10.1073/pnas.82.4.1074. View

5.
Takeshita M, Chang C, Johnson F, Will S, Grollman A . Oligodeoxynucleotides containing synthetic abasic sites. Model substrates for DNA polymerases and apurinic/apyrimidinic endonucleases. J Biol Chem. 1987; 262(21):10171-9. View