Abstract
It has been known for some time that 5-methylcytosine (5meC) in DNA is a mutation hazard, since deamination of 5meC converts it to thymine, a normal base (Lindahl and Nyberg, 1974). Replication of DNA containing such T:G mismatches results in C to T mutations. Sites of cytosine methylation were first recognized to be hotspots for transition mutations in the lacI system of E. coli (Coulondre et al., 1978), and this observation has been confirmed in other E. coli gene systems and has been extended to human cells. Transition mutations in CpG sequences are the largest class of point mutations found in genetic diseases including cancer (Cooper and Youssoufian, 1988; Greenblatt et al., 1994).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bandaru, B., et al. 1995. HpaII Methyltransferase Is Mutagenic in Escherichia coli. J. Bacteriol. 177:2950–2952.
Bhagwat, A. S., and M. McClelland. 1992. DNA mismatch correction by very short patch repair may have altered the abundance of oligonucleotides in the E. coli genome. Nucl. Acids Res. 20:1663–1668.
Cooper, D. N., and H. Youssoufian. 1988. The CpG dinucleotide and human genetic disease. Hum. Genet. 78:151–155.
Coulondre, C., et al. 1978. Molecular basis of substitution hotspots in Escherichia coli. Nature 274:775–780.
Dar, M. E., and A. S. Bhagwat. 1993. Mechanism of expression of DNA repair gene vsr, an Escherichia coli gene that overlaps the DNA cytosine methylase gene, dcm. Mol. Microbiol. 9:823–833.
Gabbara, S., et al. 1994. A DNA Repair Process in Escherichia coli Corrects U:G and T:G Mismatches to C:G at Sites of Cytosine Methylation. Molec. Gen. Genet. 243:244–248.
Gläsner, W., et al. 1992. Enzymatic Properties and Biological Functions of Vsr DNA Mismatch Endonuclease. In Structural Tools for the Analysis of Protein-Nucleic Acid Complexes, D. M. J. Lilley, H. Heumann, and D. Suck, eds. pp. 165–173. Birkhäuser Verlag Basel.
Gläsner, W., et al. 1995. Substrate Preferences of Vsr DNA Mismatch Endonuclease and their Consequences for the Evolution of the Escherichia coli K-12 Genome. J. Mol. Biol. 245:1–7.
Gomez-Eichelmann, M. C., et al., 1991. Presence of 5-Methylcytosine in CC(A/T)GG Sequences (Dem Methylation) in DNAs from Different Bacteria. J. Bacteriol. 173:7692–7694.
Greenblatt, M. S., et al. 1994. Mutations in the p53 Tumor Suppressor Gene: Clues to Cancer Etiology and Molecular Pathogenesis. Cancer Research 54:4855–4878.
Hennecke, F., et al. 1991. The vsr gene product of E. coli K-12 is a strand-and sequence-specific DNA mismatch endonuclease. Nature 353:776–778.
Lieb, M. 1983. Specific Mismatch Correction in Bacteriophage Lambda Crosses by Very Short Patch Repair. Mol. Gen. Genet. 191:118–125.
Lieb, M. 1991. Spontaneous mutation at a 5-methylcytosine hotspot is prevented by very short patch (VSP) mismatch repair. Genetics 128:23–27.
Lieb, M., et al. 1986. Very Short Patch Repair in Phage Lambda: Repair Sites and Length of Repair Tracts. Genetics 114:1041–1060.
Lieb, M., and A. S. Bhagwat. 1996. VSP: Reducing the cost of cytosine methylation. Molec. Microbiol. 20: in press.
Lieb, M., and S. Rehmat. 1995. Very short patch repair of T:G mismatches in vivo: Importance of context and accessory proteins. J. Bacteriol. 177:660–666.
Lindahl, T., and B. Nyberg. 1974. Heat-induced deamination of cytosine residues in deoxyribonucleic acid. Biochemistry 13:3405–3410.
Marinus, M. G. 1973. Location of DNA Methylation Genes on the Escherichia coli Genetic Map. Mol. Gen. Genet. 127:47–55.
Marinus, M. G., and N. R. Morris. 1973. Isolation of Deoxyribonucleic Acid Methylase Mutants of Escherichia coli K-12. J. Bacteriol. 114:1143–1150.
Markl, R., et al. 1992. Statistical evaluation and biological interpretation of nonrandom abundance in the E. coli K-12 genome of tetra-and pentanucleotide sequences related to VSP DNA mismatch repair. Nucl. Acids Res. 20:1657–1662.
Nedderman, P., and J. Jiricny. 1993. The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells. J. Biol. Chem. 268:21218–21224.
Ruiz, S. M., et al. 1993. Isolation and characterization of an Escherichia coli strain with a high frequency of C-to-T mutations at 5-methylcytosines. J. Bacteriol. 175:4985–4989.
Smith, R. F., and T. F. Smith. 1990. Automatic generation of primary sequence patterns from sets of related protein sequences. Proc. Natl. Acad. Sci. (USA) 87:118–122.
Sohail, A., et al. 1990. A Gene Required for Very Short Patch repair in E. coli is Adjacent to the DNA Cytosine Methylase Gene. J. Bacteriol. 172:4214–4221.
Wyszynski, M., et al. 1994. Cytosine Deaminations Catalyzed by DNA Cytosine Methy1-transferases are unlikely to be the Major Cause of Mutational Hot-spots at Sites of Cytosine Methylation in E. coli. Proc. Natl. Acad. Sci. (USA) 91:1574–1578.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Bhagwat, A.S., Lieb, M. (1998). Mechanism of Avoidance of 5-methylcytosine to Thymine Mutations in Bacteria. In: de Bruijn, F.J., Lupski, J.R., Weinstock, G.M. (eds) Bacterial Genomes. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6369-3_12
Download citation
DOI: https://doi.org/10.1007/978-1-4615-6369-3_12
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7925-6
Online ISBN: 978-1-4615-6369-3
eBook Packages: Springer Book Archive