Mechanism of Mutation in Non-Dividing Cells
Abstract
Stationary-phase mutation is a mutational program that can be induced in non-dividing cells after exposure to environmental stress. We tested the postulate that stationary-phase mutations result from acts of DNA double-strand break repair. In one model for stationary-phase mutation, a DSBR intermediate primes DNA synthesis, during which pol IV, an error-prone polymerase required for stationary-phase Lac+ mutation, is proposed to create errors that lead to mutation. F plasmid transfer (Tra) proteins are required for stationary-phase reversion of a +1 frameshift mutation on an F' sex plasmid. Tra functions induce single-strand nicks on the F', which could lead to DSBs. We find that introducing specific breaks on an F' that lacks Tra functions results in 50-2000-fold stimulation of Lac+ stationary-phase mutation. These results provide the first direct evidence that DNA DSBs can activate stationary-phase mutation and imply that the role of Tra functions is to promote the formation of DSBs. We report that DSB-stimulated mutation requires recombination proteins and DNA pol IV. This indicates that introduction of DSBs activates a similar mechanism to that which produces Lac+ stationary-phase mutation, and not an alternative pathway, and that the recombination and polymerase functions are required after DSB formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408728
Entities
People
- Rebecca G. Ponder
- Susan M Rosenberg
Organizations
- Baylor College of Medicine