Increased and Imbalanced dNTP Pools Symmetrically Promote Both Leading and Lagging Strand Replication Infidelity

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The building blocks of DNA, dNTPs, are vital to life, and thus their production is carefully controlled within each cell. Under certain conditions, such as cancer, infection, or drugs, the overall dNTP level or dNTP balance can change. Using yeast genetics we manipulated the dNTP pool balance in unicellular baker's yeast and analysed the effects upon fidelity of DNA replication. We also disrupted mismatch repair, an internal safety system that corrects replication errors and is mutated in many cancers. By sequencing DNA from yeast cells with these alterations we gain insights into the mechanisms of mutation formation that contribute to genome instability. We find that the leading and lagging strand replication fidelity is affected similarly by the dNTP pool imbalance and that the mismatch repair machinery corrects replication errors driven by a dNTP pool imbalance with highly variable efficiencies.

Vyšlo v časopise: Increased and Imbalanced dNTP Pools Symmetrically Promote Both Leading and Lagging Strand Replication Infidelity. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004846
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004846

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