Mechanisms of Genome‐Wide Hypermutation in Stationary Phase<sup>a</sup>

Lombardo, Mary‐Jane; Torkelson, Joel; Bull, Harold J.; McKenzie, Gregory J.; Rosenberg, Susan M.

doi:10.1111/j.1749-6632.1999.tb08888.x

Cited by 18 publications

(15 citation statements)

References 58 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If nicks at the FЈ transfer origin are the signal, this could explain why transfer (Tra) proteins (but not actual transfer) are required for efficient adaptive mutation (56,57), despite evidence that the FЈ need not be covalently linked with the DNA undergoing mutation (28,58,59). A trans role for the FЈ (also suggested by ref.…”

Section: Discussionmentioning

confidence: 99%

The SOS response regulates adaptive mutation

McKenzie

Harris

Lee

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

258

201

View full text Add to dashboard Cite

Upon starvation some Escherichia coli cells undergo a transient, genome-wide hypermutation (called adaptive mutation) that is recombination-dependent and appears to be a response to a stressful environment. Adaptive mutation may reflect an inducible mechanism that generates genetic variability in times of stress. Previously, however, the regulatory components and signal transduction pathways controlling adaptive mutation were unknown. Here we show that adaptive mutation is regulated by the SOS response, a complex, graded response to DNA damage that includes induction of gene products blocking cell division and promoting mutation, recombination, and DNA repair. We find that SOS-induced levels of proteins other than RecA are needed for adaptive mutation. We report a requirement of RecF for efficient adaptive mutation and provide evidence that the role of RecF in mutation is to allow SOS induction. We also report the discovery of an SOS-controlled inhibitor of adaptive mutation, PsiB. These results indicate that adaptive mutation is a tightly regulated response, controlled both positively and negatively by the SOS system.T he bacterial SOS response, studied extensively in Escherichia coli, is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis are induced (1). SOS is the prototypic cell cycle check-point control and DNA repair system, and because of this, a detailed picture of the signal transduction pathway that regulates this response is understood. A central part of the SOS response is the de-repression of more than 20 genes under the direct and indirect transcriptional control of the LexA repressor. The LexA regulon includes recombination and repair genes recA, recN, and ruvAB, nucleotide excision repair genes uvrAB and uvrD, the error-prone DNA polymerase (pol) genes dinB (encoding pol IV) (2) and umuDC (encoding pol V) (3), and DNA polymerase II (4, 5) in addition to many functions not yet understood. In the absence of a functional SOS response, cells are sensitive to DNA damaging agents.The signal transduction pathway leading to an SOS response (reviewed by ref. 6) ensues when RecA protein binds to singlestranded DNA (ssDNA), which can be created by processing of DNA damage, stalled replication, and perhaps by other means (7-9). The ssDNA acts as a signal that activates an otherwise dormant co-protease activity of RecA, which allows activated RecA (called RecA*) to facilitate the proteolytic self-cleavage of the LexA repressor, thus inducing the LexA regulon (10). Activated RecA also facilitates the cleavage of phage repressors used to maintain the quiescent, lysogenic state, and UmuD, creating UmuDЈ, the subunit of UmuDЈC (pol V) that allows activity in trans-lesion error-prone DNA synthesis (6).An intriguing feature of the SOS response is inducible mutation (11, 12). LexA-repressed pol V participates in most UV mutagenesis, by inserting bases across from pyrimidine dimers (3). Pol IV is required for an indirect mutation phenomenon in which undamaged phage DNA ...

show abstract

Section: Discussionmentioning

confidence: 99%

The SOS response regulates adaptive mutation

McKenzie

Harris

Lee

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

258

201

View full text Add to dashboard Cite

show abstract

“…Two studies imply that the chromosomal stationary-phase mutations form in trans to the FЈ, and not in cis, in cells that are Hfrs. First, although Hfr formation occurs measurably in this system, Lac ϩ adaptive mutants carrying a chromosomal mutation are not enriched for Hfrs (56). Thus, there is no correlation between integrating the FЈ and acquiring a chromosomal mutation.…”

Section: ϫ2mentioning

confidence: 94%

Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence

Bull

Lombardo

Rosenberg

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

104

View full text Add to dashboard Cite

Several microbial systems have been shown to yield advantageous mutations in slowly growing or nongrowing cultures. In one assay system, the stationary-phase mutation mechanism differs from growth-dependent mutation, demonstrating that the two are different processes. This system assays reversion of a lac frameshift allele on an F plasmid in Escherichia coli. The stationary-phase mutation mechanism at lac requires recombination proteins of the RecBCD double-strand-break repair system and the inducible errorprone DNA polymerase IV, and the mutations are mostly ؊1 deletions in small mononucleotide repeats. This mutation mechanism is proposed to occur by DNA polymerase errors made during replication primed by recombinational double-strand-break repair. It has been suggested that this mechanism is confined to the F plasmid. However, the cells that acquire the adaptive mutations show hypermutation of unrelated chromosomal genes, suggesting that chromosomal sites also might experience recombination protein-dependent stationary-phase mutation. Here we test directly whether the stationary-phase mutations in the bacterial chromosome also occur via a recombination protein-and pol IV-dependent mechanism. We describe an assay for chromosomal mutation in cells carrying the F lac. We show that the chromosomal mutation is recombination protein-and pol IV-dependent and also is associated with general hypermutation. The data indicate that, at least in these male cells, recombination protein-dependent stationaryphase mutation is a mechanism of general inducible genetic change capable of affecting genes in the bacterial chromosome.Escherichia coli ͉ adaptive mutation ͉ SOS response ͉ DNA repair

show abstract

“…These characteristics suggested that stationary-phase Lac ϩ reversions occur via a different molecular mechanism(s) than for those reversions of the same lac allele that are generated during growth. However, there is also evidence that demonstrates that the mutations generated by this lac system during stationary phase are the result of gene amplification followed by SOS-induced mutagenesis and selection (39).Although the very observations of adaptive or stationaryphase mutagenesis could have suggested the existence of a Lamarckian type of genetics, subsequent research has demonstrated that this type of mutagenesis is not necessarily directed only to the selected genes (17,46,73). In fact, some studies have suggested that in a starving or stressed culture, a small subpopulation of the cells seem to have an overall increased mutation frequency (5,15,33,46,73).…”

mentioning

confidence: 99%

“…In fact, some studies have suggested that in a starving or stressed culture, a small subpopulation of the cells seem to have an overall increased mutation frequency (5,15,33,46,73). Basically, the results mentioned above were used to generate a proposal suggesting that a physiologically stressed bacterial community may differentiate a hypermutable subpopulation and that these hypermutable cells generate mutations randomly.…”

mentioning

confidence: 99%

Adaptive, or Stationary-Phase, Mutagenesis, a Component of Bacterial Differentiation in Bacillus subtilis

2002

View full text Add to dashboard Cite

Adaptive (stationary-phase) mutagenesis occurs in the gram-positive bacterium Bacillus subtilis. Furthermore, taking advantage of B. subtilis as a paradigm for the study of prokaryotic differentiation and development, we have shown that this type of mutagenesis is subject to regulation involving at least two of the genes that are involved in the regulation of post-exponential phase prokaryotic differentiation, i.e., comA and comK. On the other hand, a functional RecA protein was not required for this type of mutagenesis. The results seem to suggest that a small subpopulation(s) of the culture is involved in adaptive mutagenesis and that this subpopulation(s) is hypermutable. The existence of such a hypermutable subpopulation(s) raises important considerations with respect to evolution, the development of specific mutations, the nature of bacterial populations, and the level of communication among bacteria in an ecological niche.For over a decade, there has been considerable interest in a phenomenon that has been called adaptive, or stationaryphase, mutagenesis. The result of the mechanism(s) responsible for this phenomenon is the production of mutations that arise in nondividing or stationary-phase bacteria when the cells are subjected to nonlethal selective pressure, such as nutrientlimited environments (6,11,15,32,61). While most of the research has involved Escherichia coli model systems, similar observations have been made in other prokaryotes (43) as well as in eukaryotic organisms (69).In the FЈ lac frameshift reversion assay system in E. coli, stationary-phase mutations that lead to the generation of Lac ϩ cells can be distinguished from normal growth-dependent spontaneous Lac ϩ mutations (21, 59, 63). Specifically, Lac ϩ mutations are generated in stationary-phase cells via a molecular mechanism that requires a functional homologous recombination system (11,21,36,37), FЈ transfer functions (20, 23), and a component(s) of the SOS system (50). Genetic evidence suggests that DNA polymerase III (18, 35) and DNA polymerase IV (51, 52) are responsible for the synthesis of errors that lead to these mutations. Furthermore, for the Lac ϩ mutations, different sequence spectra are generated for the stationaryphase mutations than for the types of mutations generated during growth.For instance, a majority of the Lac ϩ mutations that arise during stationary phase have a Ϫ1 deletion at mononucleotide repeats within the target gene. On the other hand, for the spontaneous mutations that arise during growth, various types of mutations occur in seemingly random locations (19, 62). These characteristics suggested that stationary-phase Lac ϩ reversions occur via a different molecular mechanism(s) than for those reversions of the same lac allele that are generated during growth. However, there is also evidence that demonstrates that the mutations generated by this lac system during stationary phase are the result of gene amplification followed by SOS-induced mutagenesis and selection (39).Although the very observations of ada...

show abstract

Mechanisms of Genome‐Wide Hypermutation in Stationary Phase^a

Cited by 18 publications

References 58 publications

The SOS response regulates adaptive mutation

The SOS response regulates adaptive mutation

Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence

Adaptive, or Stationary-Phase, Mutagenesis, a Component of Bacterial Differentiation in Bacillus subtilis

Contact Info

Product

Resources

About

Mechanisms of Genome‐Wide Hypermutation in Stationary Phasea

Cited by 18 publications

References 58 publications

The SOS response regulates adaptive mutation

The SOS response regulates adaptive mutation

Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence

Adaptive, or Stationary-Phase, Mutagenesis, a Component of Bacterial Differentiation in Bacillus subtilis

Contact Info

Product

Resources

About

Mechanisms of Genome‐Wide Hypermutation in Stationary Phase^a