Escherichia coli Strains (ndk) Lacking Nucleoside Diphosphate Kinase Are Powerful Mutators for Base Substitutions and Frameshifts in Mismatch-Repair-Deficient Strains

Corresponding author: Jeffrey H. Miller, Immunology, and Molecular Genetics, UCLA, 405 Hilgard Ave., Los Angeles, CA 90095., jhmiller{at}mbi.ucla.edu (E-mail)

Communicating editor: H. OCHMAN

Nucleoside diphosphate (NDP) kinase is one of the enzymes that maintains triphosphate pools. Escherichia coli strains (ndk) lacking this enzyme have been shown to be modest base substitution mutators, and two members of the human family of NDP kinases act as tumor suppressors. We show here that in E. coli strains lacking NDP kinase high levels of mispairs are generated, but most of these are corrected by the mismatch-repair system. Double mutants that are ndk mutS, lacking both the NDP kinase and mismatch repair, have levels of base substitutions 15-fold higher and levels of certain frameshifts up to 10-fold higher than those of the respective mutations in mutS strains that are NDP kinase proficient. A sequence analysis of the specificity of base substitution mutations generated in ndk and ndk mutS backgrounds as well as other experiments suggests that NDP kinase deficiency stimulates polymerase errors that lead to A:T G:C transitions and that the editing capacity of cells may be affected, leading to additional uncorrected mispairs and to A:T T:A transversions.

This article has been cited by other articles:

				K. Zeibell, S. Aguila, V. Yan Shi, A. Chan, H. Yang, and J. H. Miller Mutagenesis and Repair in Bacillus anthracis: the Effect of Mutators J. Bacteriol., March 15, 2007; 189(6): 2331 - 2338. [Abstract] [Full Text] [PDF]

				H. Bai and A-L. Lu Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS J. Bacteriol., February 1, 2007; 189(3): 902 - 910. [Abstract] [Full Text] [PDF]

				S. C. Goswami, J.-H. Yoon, B. M. Abramczyk, G. P. Pfeifer, and E. H. Postel Molecular and Functional Interactions between Escherichia coli Nucleoside-diphosphate Kinase and the Uracil-DNA Glycosylase Ung J. Biol. Chem., October 27, 2006; 281(43): 32131 - 32139. [Abstract] [Full Text] [PDF]

				C. K. Mathews DNA precursor metabolism and genomic stability FASEB J, July 1, 2006; 20(9): 1300 - 1314. [Abstract] [Full Text] [PDF]

				V. Gabrovsky, M. L. Yamamoto, and J. H. Miller Mutator Effects in Escherichia coli Caused by the Expression of Specific Foreign Genes J. Bacteriol., July 15, 2005; 187(14): 5044 - 5048. [Abstract] [Full Text] [PDF]

				E. S. Hong, A. Yeung, P. Funchain, M. M. Slupska, and J. H. Miller Mutants with Temperature-Sensitive Defects in the Escherichia coli Mismatch Repair System: Sensitivity to Mispairs Generated In Vivo J. Bacteriol., February 1, 2005; 187(3): 840 - 846. [Abstract] [Full Text] [PDF]

				S. E. Bennett, C.-Y. Chen, and D. W. Mosbaugh Escherichia coli nucleoside diphosphate kinase does not act as a uracil-processing DNA repair nuclease PNAS, April 27, 2004; 101(17): 6391 - 6396. [Abstract] [Full Text] [PDF]

				E. H. Postel and B. M. Abramczyk Escherichia coli nucleoside diphosphate kinase is a uracil-processing DNA repair nuclease PNAS, November 11, 2003; 100(23): 13247 - 13252. [Abstract] [Full Text] [PDF]

				M. Kim, T. Huang, and J. H. Miller Competition between MutY and Mismatch Repair at A {middle dot} C Mispairs In Vivo J. Bacteriol., August 1, 2003; 185(15): 4626 - 4629. [Abstract] [Full Text] [PDF]