title: A new proofreading mechanism for lesion bypass by DNA polymerase-λ.
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-λ, 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.
authors: Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors: Emmanuele
authors: E
authors: Crespan
authors: Giovanni
authors: G
authors: Maga
authors: Ulrich
authors: U
authors: Hübscher
mesh_terms: D053904:DNA Breaks, Single-Stranded; D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D011756:Diphosphates / Q000378:metabolism; D004789:Enzyme Activation; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans
chemical_list: D003838:Deoxyadenine Nucleotides; D011756:Diphosphates; D006151:Guanosine; C046215:8-hydroxyguanosine; C107241:diphosphoric acid; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta