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Bacterial Stationary-State Mutagenesis and Mammalian Tumorigenesis as Stress-Induced Cellular Adaptations and the Role of Epigenetics

[ Vol. 7 , Issue. 8 ]

Author(s):

T. V. Karpinets, D. J. Greenwood, I. P. Pogribny and N. F. Samatova   Pages 481 - 496 ( 16 )

Abstract:


Mechanisms of cellular adaptation may have some commonalities across different organisms. Revealing these common mechanisms may provide insight in the organismal level of adaptation and suggest solutions to important problems related to the adaptation. An increased rate of mutations, referred as the mutator phenotype, and beneficial nature of these mutations are common features of the bacterial stationary-state mutagenesis and of the tumorigenic transformations in mammalian cells. We argue that these commonalities of mammalian and bacterial cells result from their stressinduced adaptation that may be described in terms of a common model. Specifically, in both organisms the mutator phenotype is activated in a subpopulation of proliferating stressed cells as a strategy to survival. This strategy is an alternative to other survival strategies, such as senescence and programmed cell death, which are also activated in the stressed cells by different subpopulations. Sustained stress-related proliferative signalling and epigenetic mechanisms play a decisive role in the choice of the mutator phenotype survival strategy in the cells. They reprogram cellular functions by epigenetic silencing of cell-cycle inhibitors, DNA repair, programmed cell death, and by activation of repetitive DNA elements. This reprogramming leads to the mutator phenotype that is implemented by error-prone cell divisions with the involvement of Y family polymerases. Studies supporting the proposed model of stress-induced cellular adaptation are discussed. Cellular mechanisms involved in the bacterial stress-induced adaptation are considered in more detail.

Keywords:

Adaptive mutagenesis, bacteria, cancer, stress, histone-like proteins, epigenetic alterations

Affiliation:

Computational Biology Institute,Computer Science and Mathematics Division, Oak Ridge National Laboratory, P.O. Box 2008, MS6164, Oak Ridge, TN 37831, USA.



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