Abstract
Adaptive mutation has been studied extensively in FC40, a strain of Escherichia coli that cannot metabolize lactose (Lac-) because of a frameshift mutation affecting the lacZ gene on its episome. recD mutants of FC40, in which the exonuclease activity of RecBCD (ExoV) is abolished but its helicase activity is retained, have an increased rate of adaptive mutation. The results presented here show that, in several respects, adaptive mutation to Lac+ involves different mechanisms in recD mutant cells than in wild-type cells. About half of the apparent increase in the adaptive mutation rate of recD mutant cells is due to a RecA-dependent increase in episomal copy number and to growth of the Lac- cells on the lactose plates. The remaining increase appears to be due to continued replication of the episome, with the extra copies being degraded or passed to recD+ recipients. In addition, the increase in adaptive mutation rate in recD mutant cells is (i) dependent on activities of the single-stranded exonucleases, RecJ and ExoI, which are not required for (in fact, slightly inhibit) adaptive mutation in wild-type cells, and (ii) enhanced by RecG, which opposes adaptive mutation in wild-type cells.
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- Akerlund T., Nordström K., Bernander R. Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. J Bacteriol. 1995 Dec;177(23):6791–6797. doi: 10.1128/jb.177.23.6791-6797.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Al-Deib A. A., Mahdi A. A., Lloyd R. G. Modulation of recombination and DNA repair by the RecG and PriA helicases of Escherichia coli K-12. J Bacteriol. 1996 Dec;178(23):6782–6789. doi: 10.1128/jb.178.23.6782-6789.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersson D. I., Slechta E. S., Roth J. R. Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon. Science. 1998 Nov 6;282(5391):1133–1135. doi: 10.1126/science.282.5391.1133. [DOI] [PubMed] [Google Scholar]
- Asai T., Bates D. B., Kogoma T. DNA replication triggered by double-stranded breaks in E. coli: dependence on homologous recombination functions. Cell. 1994 Sep 23;78(6):1051–1061. doi: 10.1016/0092-8674(94)90279-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barton B. M., Harding G. P., Zuccarelli A. J. A general method for detecting and sizing large plasmids. Anal Biochem. 1995 Apr 10;226(2):235–240. doi: 10.1006/abio.1995.1220. [DOI] [PubMed] [Google Scholar]
- Bassett C. L., Kushner S. R. Exonucleases I, III, and V are required for stability of ColE1-related plasmids in Escherichia coli. J Bacteriol. 1984 Feb;157(2):661–664. doi: 10.1128/jb.157.2.661-664.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biek D. P., Cohen S. N. Identification and characterization of recD, a gene affecting plasmid maintenance and recombination in Escherichia coli. J Bacteriol. 1986 Aug;167(2):594–603. doi: 10.1128/jb.167.2.594-603.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns J., Foster P. L. Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics. 1991 Aug;128(4):695–701. doi: 10.1093/genetics/128.4.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns J., Overbaugh J., Miller S. The origin of mutants. Nature. 1988 Sep 8;335(6186):142–145. doi: 10.1038/335142a0. [DOI] [PubMed] [Google Scholar]
- Chaudhury A. M., Smith G. R. A new class of Escherichia coli recBC mutants: implications for the role of RecBC enzyme in homologous recombination. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7850–7854. doi: 10.1073/pnas.81.24.7850. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen A., Clark A. J. Synthesis of linear plasmid multimers in Escherichia coli K-12. J Bacteriol. 1986 Jul;167(1):327–335. doi: 10.1128/jb.167.1.327-335.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper S., Keasling J. D. Cycle-specific replication of chromosomal and F-plasmid origins. FEMS Microbiol Lett. 1998 Jun 15;163(2):217–222. doi: 10.1111/j.1574-6968.1998.tb13048.x. [DOI] [PubMed] [Google Scholar]
- Coulondre C., Miller J. H. Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues. J Mol Biol. 1977 Dec 15;117(3):525–567. doi: 10.1016/0022-2836(77)90056-0. [DOI] [PubMed] [Google Scholar]
- Foster P. L. Adaptive mutation: has the unicorn landed? Genetics. 1998 Apr;148(4):1453–1459. doi: 10.1093/genetics/148.4.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L. Adaptive mutation: the uses of adversity. Annu Rev Microbiol. 1993;47:467–504. doi: 10.1146/annurev.mi.47.100193.002343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Cairns J. Mechanisms of directed mutation. Genetics. 1992 Aug;131(4):783–789. doi: 10.1093/genetics/131.4.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Gudmundsson G., Trimarchi J. M., Cai H., Goodman M. F. Proofreading-defective DNA polymerase II increases adaptive mutation in Escherichia coli. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7951–7955. doi: 10.1073/pnas.92.17.7951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L. Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli. J Bacteriol. 1997 Mar;179(5):1550–1554. doi: 10.1128/jb.179.5.1550-1554.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L. Population dynamics of a Lac- strain of Escherichia coli during selection for lactose utilization. Genetics. 1994 Oct;138(2):253–261. doi: 10.1093/genetics/138.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Trimarchi J. M. Adaptive reversion of a frameshift mutation in Escherichia coli by simple base deletions in homopolymeric runs. Science. 1994 Jul 15;265(5170):407–409. doi: 10.1126/science.8023164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Trimarchi J. M. Adaptive reversion of an episomal frameshift mutation in Escherichia coli requires conjugal functions but not actual conjugation. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5487–5490. doi: 10.1073/pnas.92.12.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Trimarchi J. M. Conjugation is not required for adaptive reversion of an episomal frameshift mutation in Escherichia coli. J Bacteriol. 1995 Nov;177(22):6670–6671. doi: 10.1128/jb.177.22.6670-6671.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. L., Trimarchi J. M., Maurer R. A. Two enzymes, both of which process recombination intermediates, have opposite effects on adaptive mutation in Escherichia coli. Genetics. 1996 Jan;142(1):25–37. doi: 10.1093/genetics/142.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frame R., Bishop J. O. The number of sex-factors per chromosome in Escherichia coli. Biochem J. 1971 Jan;121(1):93–103. doi: 10.1042/bj1210093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedman-Ohana R., Cohen A. Heteroduplex joint formation in Escherichia coli recombination is initiated by pairing of a 3'-ending strand. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6909–6914. doi: 10.1073/pnas.95.12.6909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galitski T., Roth J. R. Evidence that F plasmid transfer replication underlies apparent adaptive mutation. Science. 1995 Apr 21;268(5209):421–423. doi: 10.1126/science.7716546. [DOI] [PubMed] [Google Scholar]
- Gordon G. S., Sitnikov D., Webb C. D., Teleman A., Straight A., Losick R., Murray A. W., Wright A. Chromosome and low copy plasmid segregation in E. coli: visual evidence for distinct mechanisms. Cell. 1997 Sep 19;90(6):1113–1121. doi: 10.1016/s0092-8674(00)80377-3. [DOI] [PubMed] [Google Scholar]
- Harris R. S., Feng G., Ross K. J., Sidhu R., Thulin C., Longerich S., Szigety S. K., Winkler M. E., Rosenberg S. M. Mismatch repair protein MutL becomes limiting during stationary-phase mutation. Genes Dev. 1997 Sep 15;11(18):2426–2437. doi: 10.1101/gad.11.18.2426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris R. S., Longerich S., Rosenberg S. M. Recombination in adaptive mutation. Science. 1994 Apr 8;264(5156):258–260. doi: 10.1126/science.8146657. [DOI] [PubMed] [Google Scholar]
- Harris R. S., Ross K. J., Rosenberg S. M. Opposing roles of the holliday junction processing systems of Escherichia coli in recombination-dependent adaptive mutation. Genetics. 1996 Mar;142(3):681–691. doi: 10.1093/genetics/142.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kogoma T., Cadwell G. W., Barnard K. G., Asai T. The DNA replication priming protein, PriA, is required for homologous recombination and double-strand break repair. J Bacteriol. 1996 Mar;178(5):1258–1264. doi: 10.1128/jb.178.5.1258-1264.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koob M., Szybalski W. Preparing and using agarose microbeads. Methods Enzymol. 1992;216:13–20. doi: 10.1016/0076-6879(92)16004-4. [DOI] [PubMed] [Google Scholar]
- Kowalczykowski S. C., Dixon D. A., Eggleston A. K., Lauder S. D., Rehrauer W. M. Biochemistry of homologous recombination in Escherichia coli. Microbiol Rev. 1994 Sep;58(3):401–465. doi: 10.1128/mr.58.3.401-465.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuzminov A. Instability of inhibited replication forks in E. coli. Bioessays. 1995 Aug;17(8):733–741. doi: 10.1002/bies.950170810. [DOI] [PubMed] [Google Scholar]
- Lanka E., Wilkins B. M. DNA processing reactions in bacterial conjugation. Annu Rev Biochem. 1995;64:141–169. doi: 10.1146/annurev.bi.64.070195.001041. [DOI] [PubMed] [Google Scholar]
- Lovett S. T., Clark A. J. Cloning of the Escherichia coli recJ chromosomal region and identification of its encoded proteins. J Bacteriol. 1985 Apr;162(1):280–285. doi: 10.1128/jb.162.1.280-285.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett S. T., Clark A. J. Genetic analysis of the recJ gene of Escherichia coli K-12. J Bacteriol. 1984 Jan;157(1):190–196. doi: 10.1128/jb.157.1.190-196.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett S. T., Kolodner R. D. Identification and purification of a single-stranded-DNA-specific exonuclease encoded by the recJ gene of Escherichia coli. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2627–2631. doi: 10.1073/pnas.86.8.2627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett S. T., Luisi-DeLuca C., Kolodner R. D. The genetic dependence of recombination in recD mutants of Escherichia coli. Genetics. 1988 Sep;120(1):37–45. doi: 10.1093/genetics/120.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovett S. T., Sutera V. A., Jr Suppression of recJ exonuclease mutants of Escherichia coli by alterations in DNA helicases II (uvrD) and IV (helD). Genetics. 1995 May;140(1):27–45. doi: 10.1093/genetics/140.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandal T. N., Mahdi A. A., Sharples G. J., Lloyd R. G. Resolution of Holliday intermediates in recombination and DNA repair: indirect suppression of ruvA, ruvB, and ruvC mutations. J Bacteriol. 1993 Jul;175(14):4325–4334. doi: 10.1128/jb.175.14.4325-4334.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marians K. J., Hiasa H., Kim D. R., McHenry C. S. Role of the core DNA polymerase III subunits at the replication fork. Alpha is the only subunit required for processive replication. J Biol Chem. 1998 Jan 23;273(4):2452–2457. doi: 10.1074/jbc.273.4.2452. [DOI] [PubMed] [Google Scholar]
- McGlynn P., Al-Deib A. A., Liu J., Marians K. J., Lloyd R. G. The DNA replication protein PriA and the recombination protein RecG bind D-loops. J Mol Biol. 1997 Jul 11;270(2):212–221. doi: 10.1006/jmbi.1997.1120. [DOI] [PubMed] [Google Scholar]
- Michel B., Ehrlich S. D., Uzest M. DNA double-strand breaks caused by replication arrest. EMBO J. 1997 Jan 15;16(2):430–438. doi: 10.1093/emboj/16.2.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Modrich P., Lahue R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem. 1996;65:101–133. doi: 10.1146/annurev.bi.65.070196.000533. [DOI] [PubMed] [Google Scholar]
- Nurse P., Zavitz K. H., Marians K. J. Inactivation of the Escherichia coli priA DNA replication protein induces the SOS response. J Bacteriol. 1991 Nov;173(21):6686–6693. doi: 10.1128/jb.173.21.6686-6693.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peters J. E., Bartoszyk I. M., Dheer S., Benson S. A. Redundant homosexual F transfer facilitates selection-induced reversion of plasmid mutations. J Bacteriol. 1996 Jun;178(11):3037–3043. doi: 10.1128/jb.178.11.3037-3043.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Razavy H., Szigety S. K., Rosenberg S. M. Evidence for both 3' and 5' single-strand DNA ends in intermediates in chi-stimulated recombination in vivo. Genetics. 1996 Feb;142(2):333–339. doi: 10.1093/genetics/142.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rinken R., Thomas B., Wackernagel W. Evidence that recBC-dependent degradation of duplex DNA in Escherichia coli recD mutants involves DNA unwinding. J Bacteriol. 1992 Aug;174(16):5424–5429. doi: 10.1128/jb.174.16.5424-5429.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandler S. J., Samra H. S., Clark A. J. Differential suppression of priA2::kan phenotypes in Escherichia coli K-12 by mutations in priA, lexA, and dnaC. Genetics. 1996 May;143(1):5–13. doi: 10.1093/genetics/143.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seelke R., Kline B., Aleff R., Porter R. D., Shields M. S. Mutations in the recD gene of Escherichia coli that raise the copy number of certain plasmids. J Bacteriol. 1987 Oct;169(10):4841–4844. doi: 10.1128/jb.169.10.4841-4844.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seigneur M., Bidnenko V., Ehrlich S. D., Michel B. RuvAB acts at arrested replication forks. Cell. 1998 Oct 30;95(3):419–430. doi: 10.1016/s0092-8674(00)81772-9. [DOI] [PubMed] [Google Scholar]
- Shurvinton C. E., Lloyd R. G., Benson F. E., Attfield P. V. Genetic analysis and molecular cloning of the Escherichia coli ruv gene. Mol Gen Genet. 1984;194(1-2):322–329. doi: 10.1007/BF00383535. [DOI] [PubMed] [Google Scholar]
- Stetson H., Somerville R. L. Expression of the tryptophan operon in merodiploids of Escherichia coli. I. Gene dosage, gene position and marker effects. Mol Gen Genet. 1971;111(4):342–351. doi: 10.1007/BF00569786. [DOI] [PubMed] [Google Scholar]
- Tlsty T. D., Albertini A. M., Miller J. H. Gene amplification in the lac region of E. coli. Cell. 1984 May;37(1):217–224. doi: 10.1016/0092-8674(84)90317-9. [DOI] [PubMed] [Google Scholar]
- Torkelson J., Harris R. S., Lombardo M. J., Nagendran J., Thulin C., Rosenberg S. M. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. EMBO J. 1997 Jun 2;16(11):3303–3311. doi: 10.1093/emboj/16.11.3303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- West S. C. Processing of recombination intermediates by the RuvABC proteins. Annu Rev Genet. 1997;31:213–244. doi: 10.1146/annurev.genet.31.1.213. [DOI] [PubMed] [Google Scholar]