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A new proofreading mechanism for lesion bypass by DNA polymerase‐λ
Author(s) -
Crespan Emmanuele,
Maga Giovanni,
Hübscher Ulrich
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.226
Subject(s) - proofreading , exonuclease , dna polymerase , klenow fragment , dna polymerase ii , dna clamp , dna , guanine , biology , polymerase , dna replication , dna repair , dna synthesis , biochemistry , chemistry , microbiology and biotechnology , nucleotide , polymerase chain reaction , gene , reverse transcriptase
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.