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Publication Abstract from PubMed

Human DNA polymerase iota (hPoliota), a member of the Y family of DNA polymerases, differs in remarkable ways from other DNA polymerases, incorporating correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. We present here the crystal structure of hPoliota bound to template G and incoming dCTP, which reveals a G.C + Hoogsteen base pair in a DNA polymerase active site. We show that the hPoliota active site has evolved to favor Hoogsteen base pairing, wherein the template sugar is fixed in a cavity that reduces the C1'-C1' distance across the nascent base pair from approximately 10.5 A in other DNA polymerases to 8.6 A in hPoliota. The rotation of G from anti to syn is then largely in response to this curtailed C1'-C1' distance. A G.C+ Hoogsteen base pair suggests a specific mechanism for hPoliota's ability to bypass N(2)-adducted guanines that obstruct replication.

Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair.,Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK Structure. 2005 Oct;13(10):1569-77. PMID:16216587^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.