4.7 Review

DNA damage bypass pathways and their effect on mutagenesis in yeast

Journal

FEMS MICROBIOLOGY REVIEWS
Volume 45, Issue 1, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/femsre/fuaa038

Keywords

Saccharomyces cerevisiae; DNA damage; PCNA; post-replication repair; DNA damage tolerance; homologous recombination; mutation

Categories

Funding

  1. Israel Science Foundation
  2. Israel Cancer Research Fund
  3. Minerva Center for in-lab Evolution (Minerva Stiftung)

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The origin of mutations is not random, but largely caused by genetically encoded error-prone repair mechanisms. Cells are still unclear about when to use which repair method. For the yeast Saccharomyces cerevisiae, at least two error-free and two error-prone inter-related mechanisms of damage tolerance have been identified.
What is the origin of mutations? In contrast to the naive notion that mutations are unfortunate accidents, genetic research in microorganisms has demonstrated that most mutations are created by genetically encoded error-prone repair mechanisms. However, error-free repair pathways also exist, and it is still unclear how cells decide when to use one repair method or the other. Here, we summarize what is known about the DNA damage tolerance mechanisms (also known as post-replication repair) for perhaps the best-studied organism, the yeast Saccharomyces cerevisiae. We describe the latest research, which has established the existence of at least two error-free and two error-prone inter-related mechanisms of damage tolerance that compete for the handling of spontaneous DNA damage. We explore what is known about the induction of mutations by DNA damage. We point to potential paradoxes and to open questions that still remain unanswered.

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