Mechanisms of Mutation in Non-Dividing Cells
Abstract
Understanding how mutations arise in non-growing cells will help illuminate mechanisms of oncogenesis, tumor progression, and resistance to chemotherapeutic drugs. To this end, I have been addressing how antibiotic resistance mutations occur in non-, or slowly-growing enterobacteria cells. Previously, our laboratory discovered that RecA (an hRAD51 homolog) and RecBCD recombination repair proteins are necessary for the acquisition of 13-lactam drug-resistant mutations in the Escherichia coli chromosome during stationary-phase. The data suggest that either the SOS DNA damage-repair response, recombinational DNA repair, or both, are involved in the mutation pathway. I have improved the E. coli-based system to examine the genetic and biochemical processes involved in this mutational mechanism in detail. Initial results in this improved system suggest that 13-lactam resistance mutations occur not only in a growth-dependent manner but also in response to stress induced by starvation. The starvation conditions may mimic the environment pathogens or tumor cells may encounter in inflicted patients under stress, chemotherapeutic treatment, or other anti-tumor drug regimen in which cells are in a state of slow, or non-growth. In addition, I have engineered a reporter construct that will allow me to enrich for those cells undergoing stationary-phase mutation so I may study the genetic and biochemical intermediates involved in this mutation mechanism.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA406067
Entities
People
- Joseph F. Petrosino
Organizations
- Baylor College of Medicine