Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity

Fijałkowska, Iwona J.; Dunn, Ronnie L.; Schaaper, Roel M.

doi:10.1128/jb.179.23.7435-7445.1997

Cited by 116 publications

(138 citation statements)

References 76 publications

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“…As discussed above, Pol z can perform such extension from mismatches e¤ciently. A similar suggestion was made by Roel Schaaper and co-workers (Fijalkowska et al 1997) to explain the enhanced spontaneous mutagenesis resulting from derepression of the SOS regulon in E. coli. Such a viewpoint is much more in keeping with the changing perspective on DNA repair and damage tolerance systems that has been emerging over the last few years.…”

Section: Biological Functions Of Dna Polymerase Zetamentioning

confidence: 76%

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Lawrence

Maher

2001

Phil. Trans. R. Soc. Lond. B

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DNA polymerase zeta (Pol z) and Rev1p carry out translesion replication in budding yeast, Saccharomyces cerevisiae, and are jointly responsible for almost all base pair substitution and frameshift mutations induced by DNA damage in this organism. In addition, Pol z is responsible for the majority of spontaneous mutations in yeast and has been proposed as the enzyme responsible for somatic hypermutability. Pol z, a non-processive enzyme that lacks a 3' to 5' exonuclease proofreading activity, is composed of Rev3p, the catalytic subunit, and a second subunit encoded by REV7. In keeping with its role, extension by Pol z is relatively tolerant of abnormal DNA structure at the primer terminus and is much more capable of extension from terminal mismatches than yeast DNA polymerase alpha (Pol a). Rev1p is a bifunctional enzyme that possesses a deoxycytidyl transferase activity that incorporates deoxycytidyl opposite abasic sites in the template and a second, at present poorly de¢ned, activity that is required for the bypass of a variety of lesions as well as abasic sites. Human homologues of the yeast REV1 and REV3 have been identi¢ed and, based on the phenotype of cells producing antisense RNA to one or other of these genes, their products appear also to be employed in translation replication and spontaneous mutagenesis. We suggest that Pol z is best regarded as a replication enzyme, albeit one that is used only intermittently, that promotes extension at forks the progress of which is blocked for any reason, whether the presence of an unedited terminal mismatch or unrepaired DNA lesion.

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Section: Biological Functions Of Dna Polymerase Zetamentioning

confidence: 76%

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Lawrence

Maher

2001

Phil. Trans. R. Soc. Lond. B

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“…This mutator enzyme exhibits weak polymerase activity in the absence of RecA, SSB, and ␤͞␥ complex (12,19,26). It might be present primarily, if not solely, to copy damaged DNA, although pol V could also play a role during evolution by generating untargeted mutations on undamaged DNA (21,43). pol V copies TT cis-syn photodimers, TT (6-4) photoproducts, and abasic moieties efficiently and with the same nucleotide incorporation specificity observed in vivo (19).…”

Section: Future Perspectivesmentioning

confidence: 99%

“…2e). However, pol V-catalyzed mutations on undamaged DNA, i.e., untargeted mutations, do occur (21). Thus, on the other side of the coin, the replacement of pol V with pol III once TLS is completed also remains to be determined.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli

Pham

Rangarajan

Woodgate

et al. 2001

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

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DNA polymerase V, composed of a heterotrimer of the DNA damage-inducible UmuC and UmuD 2 proteins, working in conjunction with RecA, single-stranded DNA (ssDNA)-binding protein (SSB), ␤ sliding clamp, and ␥ clamp loading complex, are responsible for most SOS lesion-targeted mutations in Escherichia coli, by catalyzing translesion synthesis (TLS). DNA polymerase II, the product of the damage-inducible polB (dinA ) gene plays a pivotal role in replication-restart, a process that bypasses DNA damage in an error-free manner. Replication-restart takes place almost immediately after the DNA is damaged (Ϸ2 min post-UV irradiation), whereas TLS occurs after pol V is induced Ϸ50 min later. We discuss recent data for pol V-catalyzed TLS and pol II-catalyzed replicationrestart. Specific roles during TLS for pol V and each of its accessory factors have been recently determined. Although the precise molecular mechanism of pol II-dependent replication-restart remains to be elucidated, it has recently been shown to operate in conjunction with RecFOR and PriA proteins.T wo seemingly unconnected questions arising during the early and mid 1970s were to decipher the biochemical basis of SOS mutagenesis in Escherichia coli, often referred to as SOS errorprone repair (1), and to determine a cellular role for E. coli DNA polymerase II. A tentative link between the two was established when it was determined that pol II was induced as part of the LexA-regulon (2). pol II was subsequently shown to be encoded by the DNA damage-inducible polB (dinA) gene (3-5). A ⌬polB strain shows no measurable UV sensitivity, and SOS-induced mutagenesis occurs at normal levels (6, 7). However, a ⌬polB ⌬umuDC double mutant strain is more sensitive to killing by UV light than either of the single mutant strains, implying that the two SOS-induced polymerases might play compensatory roles in vivo (8).The ability of pols II and V to complement each other does not mean that these activities are functionally redundant, and indeed they are not. pol V is able to copy UV-damaged DNA in a process referred to as error-prone translesion synthesis (TLS). TLS generates mutations targeted specifically to DNA template damage sites (9-12). In contrast, pol II copies chromosomal DNA during error-free replication-restart (8). Although both polymerases are induced by DNA damage, they appear to function on widely disparate time frames-pol II-catalyzed replication-restart occurs 2 min post-UV irradiation whereas pol V-catalyzed TLS begins roughly 50 min later (8). In this paper, we discuss current models for the roles of pol V in TLS and pol II in replication-restart.Coping with DNA Damage in E. coli There are over 40 genes induced on DNA damage in E. coli that have been identified recently by using microarray chip technology (13), of which at least 31 are known to be negatively regulated at the transcriptional level by the LexA protein (14). Many of these genes encode proteins required to repair DNA damage (15). The overriding importance of DNA repair is apparent from the ob...

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“…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).…”

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confidence: 99%

The SOS response regulates adaptive mutation

McKenzie

Harris

Lee

et al. 2000

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

258

201

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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 ...

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Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity

Cited by 116 publications

References 76 publications

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli

The SOS response regulates adaptive mutation

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