Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
EMBO Rep. 2011 Dec 23;13(1):68-74. doi: 10.1038/embor.2011.226.
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.
复制 DNA 聚合酶(DNA pol)通过其 3'→5'外切核酸酶活性去除错配的核苷酸,从而提高其保真度。外切核酸酶活性降低了跨损伤合成(TLS)的效率,而 TLS DNA pol 缺乏 3'→5'外切核酸酶活性。在这里,我们表明生理浓度的焦磷酸(PP(i))激活了 DNA pol-λ 的焦磷酸解活性,允许优先切除与 7,8-二氢-8-氧鸟嘌呤损伤错配的 A,或与 6-甲基鸟嘌呤错配的 T,相对于正确的 C。这是在 TLS 过程中使用替代校对机制的第一个例子。