Genome-wide analysis of the specificity and mechanisms of replication infidelity driven by imbalanced dNTP pools.

ABSTRACT: The absolute and relative concentrations of the four dNTPs are key determinants of DNA replication fidelity, yet the consequences of altered dNTP pools on replication fidelity have not previously been investigated on a genome-wide scale. Here, we use deep sequencing to determine the types, rates and locations of uncorrected replication errors that accumulate in the nuclear genome of a mismatch repair-deficient diploid yeast strain with elevated dCTP and dTTP concentrations. These imbalanced dNTP pools promote replication errors in specific DNA sequence motifs suggesting increased misinsertion and increased mismatch extension at the expense of proofreading. Interestingly, substitution rates are similar for leading and lagging strand replication, but are higher in regions replicated late in

SUBMITTER: Watt DL 

PROVIDER: S-EPMC4770217 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature