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A new proofreading mechanism for lesion bypass by DNA polymerase-?.


ABSTRACT: Replicative DNA polymerases (DNA pols) increase their fidelity by removing misincorporated nucleotides with their 3' ? 5' exonuclease activity. Exonuclease activity reduces translesion synthesis (TLS) efficiency and TLS DNA pols lack 3' ? 5' exonuclease activity. Here we show that physiological concentrations of pyrophosphate (PP(i)) activate the pyrophosphorolytic activity by DNA pol-?, allowing the preferential excision of the incorrectly incorporated A opposite a 7,8-dihydro-8-oxoguanine lesion, or T opposite a 6-methyl-guanine, with respect to the correct C. This is the first example of an alternative proofreading mechanism used during TLS.

SUBMITTER: Crespan E 

PROVIDER: S-EPMC3246252 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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A new proofreading mechanism for lesion bypass by DNA polymerase-λ.

Crespan Emmanuele E   Maga Giovanni G   Hübscher Ulrich U  

EMBO reports 20111223 1


Replicative DNA polymerases (DNA pols) increase their fidelity by removing misincorporated nucleotides with their 3' → 5' exonuclease activity. Exonuclease activity reduces translesion synthesis (TLS) efficiency and TLS DNA pols lack 3' → 5' exonuclease activity. Here we show that physiological concentrations of pyrophosphate (PP(i)) activate the pyrophosphorolytic activity by DNA pol-λ, allowing the preferential excision of the incorrectly incorporated A opposite a 7,8-dihydro-8-oxoguanine lesi  ...[more]

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