TABLE 2.

Common elements between various stress-induced mutagenesis pathways/mechanisms

Components	Organism	Mutation Assay	Reference
Stress responses
Requirement for σS/RpoS general stress response	E. coli	Stress-induced point mutation, Lac assay	(Layton and Foster, 2003; Lombardo et al., 2004)
	E. coli	Stress-induced amplification, Lac assay	(Lombardo et al., 2004)
	E. coli	DSBR-associated tetA-frameshift-reversion mutation1	(Ponder et al., 2005)
	E. coli natural isolate	Mutagenesis in aging colonies (MAC)	(Bjedov et al., 2003)
	E. coli	Starvation-induced Mu excisions	(Gomez-Gomez et al., 1997; Lamrani et al., 1999)
	P. putida	Starvation-induced Phe+ point mutations	(Saumaa et al., 2002)
	P. putida	Starvation-induced Tn4652 transposition	(Ilves et al., 2001)
Requirement for decreased function of σS/RpoS general stress response	E. coli	GASP mutations2	(Zambrano et al., 1993)
SOS DNA damage response	E. coli	Stress-induced point mutation, Lac assay	(McKenzie et al., 2000)
	E. coli	Mutagenesis in aging colonies (MAC) in laboratory strain	(Taddei et al., 1995)
	E. coli	Ciprofloxacin-induced resistance mutations in E. coli	(Cirz et al., 2005)
Rad9/Rad17/Rad24 DNA-damage checkpoint	yeast	Telomere-shortening-stress-induced retrotransposition of Ty element	(Scholes et al., 2003)
ComAK competence differentiation/starvation-stress response	B. subtilis	Starvation-induced reversion of amino acid auxotrophy	(Sung and Yasbin, 2002)
Stringent response to amino acid starvation (ppGpp synthesis)	E. coli	Amino acid-starvation-induced, transcription-associated mutagenesis	(Wright et al., 1999)
	B. subtilis	Amino acid-starvation-induced mutagenesis	(Rudner et al., 1999)
Cyclic AMP/release from catabolite repression starvation response	E. coli	Mutagenesis in aging colonies (MAC) in laboratory strain	(Taddei et al., 1995)
	E. coli	Starvation-induced Mu excisions	(Lamrani et al., 1999)
PhoPQ regulon3	E. coli	Starvation-induced mutations in the ebgR gene	(Hall, 1998)
Transcriptional repression by Mad1/Max and Mnt/Max complexes, which down-regulate genes in response to growth arrest	Human	Hypoxia-induced transcriptional down-regulation of MLH1/mismatch-repair function in human cells causing genetic (dinucleotide-repeat) instability	(Bindra and Glazer, 2007a; Mihaylova et al., 2003)
HIF-1alpha hypoxia-stress response and p53 DNA-damage response	Human	Hypoxia-induced transcriptional down-regulation of MSH2 and MSH6 mismatch-repair genes in human cells causing genetic (dinucleotide-repeat) instability	(Koshiji et al., 2005)
E2F4/p130-mediated transcriptional repression (response to radiation and oxidative damage and hypoxia stress)	Human	Hypoxia-induced down-regulation of RAD51, BRCA1 and DSBR via HR presumably leading to genome instability in human cells via NHEJ substituting in DSBR	(Bindra et al., 2005; Bindra and Glazer, 2007b)
Specialized DNA polymerases
DinB/Pol IV and other Y-family polymerases	E. coli	Stress-induced point mutation, Lac assay (DinB)	(Foster, 2000; McKenzie et al., 2001)
	E. coli	Ciprofloxacin-induced resistance mutations, requiring three SOS-inducible DNA polymerases, two in the Y-family: DinB/Pol IV and UmuD’C/PolV	(Cirz et al., 2005)
	P. putida	Starvation-induced Phe+ point mutations (DinB homologue)	(Tegova et al., 2004)
	B. subtilis	Starvation-induced reversion of amino acid auxotrophy (DinB homologue)	(Sung et al., 2003)
Pol II	E. coli natural isolate	Mutagenesis in aging colonies (MAC)	(Bjedov et al., 2003)
	E. coli	Ciprofloxacin-induced resistance mutations, requiring SOS-inducible DNA Pols II, IV and V	(Cirz et al., 2005)
Pol I	E. coli	Stress-induced amplification, Lac assay	(Hastings et al., 2004)
	E. coli	Mutagenesis in aging colonies (MAC) in laboratory strain	(Taddei et al., 1997a)
Rev3/DNA Pol zeta	S. cerevisiae	Mutations associated with DNA DSB repair via homologous recombination4	(Holbeck and Strathern, 1997)
Limiting Mismatch Repair Function
MutL/MLH1 the limiting component	E. coli	Stress-induced point mutation, Lac assay	(Harris et al., 1997, 1999)
	Human	Mutations induced by hypoxia in human cells, MLH1 transcriptionally down-regulated	(Mihaylova et al., 2003)
MutS/MSH2/MSH6 the limiting component	E. coli natural isolate	Mutagenesis in aging colonies (MAC)	(Bjedov et al., 2003)
	B. subtilis	Starvation-induced reversion of amino acid auxotrophy	(Pedraza-Reyes and Yasbin, 2004)
	E. coli	Decreased mismatch repair of heteroduplexes in phage DNA in stationary-phase cells	(Brégeon et al., 1999)
	Human	Dinucleotide instability in human cells, MSH2 and MSH6 transcriptionally down-regulated	(Koshiji et al., 2005; To et al., 2005)
MutH a minor limiting component	E. coli	Decreased mismatch repair of heteroduplexes in phage DNA in stationary-phase cells	(Brégeon et al., 1999)
DNA Repair and Recombination
RecA/Rad51	E. coli	Stress-induced point mutation, Lac assay	(Cairns and Foster, 1991; Harris et al., 1994)
	E. coli	Stress-induced amplification, Lac assay	(Slack et al., 2006)
	E. coli	Ciprofloxacin-induced resistance mutations	(Cirz et al., 2005)
	E. coli	Mutagenesis in aging colonies (MAC) in laboratory strain	(Taddei et al., 1995, 1997a)
	S. cerevisiae	Mutations associated with DNA DSB repair via homologous recombination4	(Strathern et al., 1995)
Down-regulation of RecA homologue RAD51 required	Human	Hypoxia-induced down-regulation of homologous recombination, presumably leading to genome instability	(Bindra et al., 2005)
RecBCD	E. coli	Stress-induced point mutation, Lac assay	(Harris et al., 1994)
	E. coli	Stress-induced amplification, Lac assay	(Slack et al., 2006)
	E. coli	Ciprofloxacin-induced resistance mutations	(Cirz et al., 2005)
	E. coli	Mutagenesis in aging colonies (MAC) in laboratory strain	(Taddei et al., 1997a)
RuvABC	E. coli	Stress-induced point mutation, Lac assay	(Foster et al., 1996; Harris et al., 1996)
	E. coli	Stress-induced amplification, Lac assay	(Slack et al., 2006)
	E. coli	Ciprofloxacin-induced resistance mutations	(Cirz et al., 2005)
Ku/NHEJ proteins	S. cerevisiae	Stress-induced amino acid-auxotrophy reversion	(Heidenreich et al., 2003)
	Human	Presumed for hypoxia-induced genome instability in human cells caused by NHEJ substituting for homologous recombination in DSBR due to down-regulation of RAD51 and BRCA1	(Bindra et al., 2005)
Localized Mutagenesis Processes?
Mutational clustering of unknown mechanisms	Mouse	Temporally and spatially clustered spontaneous mutations in mouse somatic cells5	(Wang et al., 2007)
	Many organisms	Multiple lines of evidence for clustering of mutations in many diverse organisms and in vitro5	(Drake et al., 2005; Drake 2007)
Mutagenesis associated with DSB repair	E. coli	Stress-induced point mutation, Lac assay	(Ponder et al., 2005)
	E. coli	Stress-induced amplification, Lac assay	(Ponder et al., 2005; Slack et al., 2006)
	E. coli	Presumed for ciprofloxacin-induced resistance mutations	(Cirz et al., 2005)
	S. cerevisiae	Mutations associated with DNA double-strand-break repair via homologous recombination4	(Strathern et al., 1995)
	S. cerevisiae	Presumed for stress-induced amino acid auxotrophy reversion dependent on Ku/NHEJ proteins	(Heidenreich et al., 2003)
	Human	Presumed for hypoxia-induced genome instability in human cells caused by NHEJ substituting for homologous recombination in DSBR due to down-regulation of RAD51 and BRCA1	(Bindra et al., 2005; Bindra et al., 2004)
Mutagenesis associated with nucleotide-excision repair (NER)	E. coli	Suggested for mutagenesis in aging colonies (MAC) assay based on requirement for UvrB NER protein	(Taddei et al., 1997a)
Mutagenesis associated with transcription	S. cerevisiae	Increased mutation in highly transcribed genes5	(Datta and Jinks-Robertson, 1995)
	E. coli	Amino acid-starvation-induced, transcription-associated mutagenesis	(Wright et al., 1999)
	E. coli	Transcription-coupled-repair-associated mutations suggested by genome sequence data	(Francino et al., 1996)
	B. subtilis	Possible transcription association implied by the requirement for the transcription-coupled-nucleotide-excision-repair factor, Mfd, for these stress-induced mutations.	(Ross et al., 2006).

¹These mutations associated with repair of a restriction-enzyme-produced DSB in vivo can form only if the cells are in stationary phase or if RpoS is expressed inappropriately in the log phase (implying that RpoS expression in stationary phase accounts for the stationary-phase specificity of the mutagenesis) (see Figure 4).

²GASP (Growth Advantage in Stationary Phase) mutations are not demonstrated to be stress-induced mutations, but might possibly be. They are mutations that confer increased fitness that allows stationary-phase stressed cells to out-compete neighboring cells. It has not been determined whether the mutations occur before or after the cells enter stationary phase (the stress condition). Mutations that partly diminish function of σ^S arise early in the GASP process and confer a fitness advantage.

³PhoPQ are part of a two-component transcriptional regulatory system involved with scavenging phosphorus and magnesium and are implicated in stress responses partly because they stabilize RpoS (Tu et al., 2006).

⁴These mutations are not known to be starvation- stationary-phase- or stress-associated. Whether stress or stationary phase were involved the activity of this DSBR-associated mutagenesis mechanism was not examined.

⁵Not known to be stress-associated.