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Biochemistry. 2011 Feb 22;50(7):1135-42. doi: 10.1021/bi101915z. Epub 2011 Jan 26.

Unlocking the sugar "steric gate" of DNA polymerases.

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  • 1Department of Biochemistry, Ohio State University, Columbus, Ohio 43210, United States.


To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2'-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the "steric gate", establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review.

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