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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Structural Basis Of Error-Prone Replication And Stalling At A Thymine Base By Human Dna Polymerase Iota, Kevin N. Kirouac, Hong Ling Jun 2009

Structural Basis Of Error-Prone Replication And Stalling At A Thymine Base By Human Dna Polymerase Iota, Kevin N. Kirouac, Hong Ling

Biochemistry Publications

Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and …


Ab Initio Exon Definition Using An Information Theory-Based Approach, Peter K. Rogan Mar 2009

Ab Initio Exon Definition Using An Information Theory-Based Approach, Peter K. Rogan

Biochemistry Publications

Transcribed exons in genes are joined together at donor and acceptor splice sites precisely and efficiently to generate mRNAs capa ble of being translated into proteins. The sequence variability in individual splice sites can be modeled using Shannon information theory. In the laboratory, the degree of individual splice site use is inferred from the structures of mRNAs and their relative abundance. These structures can be predicted using a bipartite information theory framework that is guided by current knowledge of biological mechanisms for exon recognition. We present the results of this analysis for the complete dataset of all expressed human exons.