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- Signification and Application of Mutator and Antimutator Phenotype‑Induced Genetic Variations in Evolutionary Adaptation and Cancer Therapeutics
- Woo-Hyun Chung
- J. Microbiol. 2023;61(12):1013-1024. Published online December 15, 2023
- DOI: https://doi.org/10.1007/s12275-023-00091-z
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Abstract
- Mutations present a dichotomy in their implications for cellular processes. They primarily arise from DNA replication errors or damage repair processes induced by environmental challenges. Cumulative mutations underlie genetic variations and drive evolution, yet also contribute to degenerative diseases such as cancer and aging. The mutator phenotype elucidates the heightened mutation rates observed in malignant tumors. Evolutionary adaptation, analogous to bacterial and eukaryotic systems, manifests through mutator phenotypes during changing environmental conditions, highlighting the delicate balance between advantageous mutations and their potentially detrimental consequences. Leveraging the genetic tractability of Saccharomyces cerevisiae offers unique insights into mutator phenotypes and genome instability akin to human cancers. Innovative reporter assays in yeast model organisms enable the detection of diverse genome alterations, aiding a comprehensive analysis of mutator phenotypes. Despite significant advancements, our understanding of the intricate mechanisms governing spontaneous mutation rates and preserving genetic integrity remains incomplete. This review outlines various cellular pathways affecting mutation rates and explores the role of mutator genes and mutation-derived phenotypes, particularly prevalent in malignant tumor cells. An in-depth comprehension of mutator and antimutator activities in yeast and higher eukaryotes holds promise for effective cancer control strategies.
Research Support, U.S. Gov't, Non-P.H.S.
- Utilization of Putrescine by Streptococcus pneumoniae During Growth in Choline-limited Medium
- D. Ware , J. Watt , E. Swiatlo
- J. Microbiol. 2005;43(5):398-405.
- DOI: https://doi.org/2284 [pii]
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Abstract
- Polyamines such as putrescine are small, ubiquitous polycationic molecules that are required for optimal growth of eukaryotic and prokaryotic cells. These molecules have diverse effects on cell physiology and their intracellular content is regulated by de novo synthesis and uptake from the environment. The studies presented here examined the structure of a putative polyamine transporter (Pot) operon in Streptococcus pneumoniae (pneumococcus) and growth of pneumococci in medium containing putrescine substituted for choline. RT-PCR experiments demonstrated that the four genes encoding the Pot system are co-transcribed with murB, a gene involved in an intermediary step of peptidoglycan synthesis. Pneumococci grown in chemically-defined media (CDM) containing putrescine without choline enter logarithmic phase growth after 36-48 hs. However, culture density at stationary phase eventually reaches that of choline-containing medium. Cells grown in CDM-putrescine formed abnormally elongated chains in which the daughter cells failed to separate and the choline-binding protein PspA was no longer cell-associated. Experiments with CDM containing radiolabeled putrescine demonstrated that pneumococci concentrate this polyamine in cell walls. These data suggest that pneumococci can replicate without choline if putrescine is available and this polyamine may substitute for aminoalcohols in the cell wall teichoic acids.
- Polyamine Stimulation of arcA Expression in Escherichia coli
- Mun Su Rhee , Young Sik Kim , Seon Young Park , Myung Hun Choi , Bo Min Kim , Seong Uk Kang , Kui Joo Lee , Jong Ho Lee
- J. Microbiol. 2002;40(4):305-312.
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Abstract
- The effects of two natural polyamines (putrescine and spermidine) on the synthesis of ArcA, a response regulator of the Arc two-component signal transduction system, were studied using an E. coli mutant deficient in polyamine biosynthesis. Endogenous polyamine deficiency of the mutant resulted in marked reduction in the ArcA level determined by Western blot analysis. Putrescine supplement to the growth medium effectively increased the ArcA level of the mutant in a concentration-dependent manner. Spermidine also stimulated the ArcA level in the mutant to a greater degree than putrescine. Expression of arcA'::lacZ operon fusion in the mutant was stimulated 6-fold and 10-fold by putrescine and spermidine at a 1mM concentration, respectively, indicating that the stimulatory effect of the polyamines on ArcA synthesis is due to transcriptional induction, and that spermidine is a more potent arcA inducer than putrescine. The polyamine-dependent arcA'::lacZ induction was growth-phase-dependent and independent of either arcA or fnr which are two regulators involved in anaerobic stimulation of the ArcA level. These results suggested that putrescine and spermidine polyamines may be potential intracellular signal molecules in the control of arcA expression, and thereby may play an important role in cellular metabolism.
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