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Human DNA polymerase-ι (Polι) incorporates correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. In fact, the fidelity opposite template T is so poor that Polι inserts an incorrect dGTP approximately 10 times better than it inserts the correct dATP. We determine here how a template T/U is accommodated in the Polι active site and...
Abasic sites are among the most abundant DNA lesions formed in human cells, and they present a strong block to replication. DNA polymerase ι (Polι) is one of the few DNA Pols that does not follow the A-rule opposite an abasic site. We present here three structures of human Polι in complex with DNAs containing an abasic lesion and dGTP, dTTP, or dATP as the incoming nucleotide. The structures reveal...
Acrolein is generated as the end product of lipid peroxidation and is also a ubiquitous environmental pollutant. Its reaction with the N 2 of guanine leads to a cyclic γ-HOPdG adduct that presents a block to normal replication. We show here that yeast Rev1 incorporates the correct nucleotide C opposite a permanently ring-closed form of γ-HOPdG (PdG) with nearly the same efficiency as opposite...
DNA recognition by proteins is essential for specific expression of genes in a living organism. En route to a target DNA site, a protein will often sample noncognate DNA sites through nonspecific protein-DNA interactions, resulting in a variety of conformationally different binding states. We present here the crystal structure of endonuclease BstYI bound to a noncognate DNA. Surprisingly, the structure...
Substrate-induced conformational change of the protein is the linchpin of enzymatic reactions. Replicative DNA polymerases, for example, convert from an open to a closed conformation in response to dNTP binding. Human DNA polymerase-ι (hPolι), a member of the Y family of DNA polymerases, differs strikingly from other polymerases in its much higher proficiency and fidelity for nucleotide incorporation...
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