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The MutL ATPase is required for mismatch repair.

Publication ,  Journal Article
Spampinato, C; Modrich, P
Published in: J Biol Chem
March 31, 2000

Members of the MutL family contain a novel nucleotide binding motif near their amino terminus, and the Escherichia coli protein has been found to be a weak ATPase (Ban, C., and Yang, W. (1998) Cell 95, 541-552). Genetic analysis has indicated that substitution of Lys for Glu-32 within this motif of bacterial MutL results in a strong dominant negative phenotype (Aronshtam, A., and Marinus, M. G. (1996) Nucleic Acids Res. 24, 2498-2504). By in vitro comparison of MutL-E32K with the wild type protein, we show the mutant protein to be defective in DNA-activated ATP hydrolysis, as well as MutS- and MutL-dependent activation of the MutH d(GATC) endonuclease and the mismatch repair excision system. MutL-E32K also acts in dominant negative manner in the presence of wild type MutL in vitro, inhibiting the overall mismatch repair reaction, as well as MutH activation. As judged by protein affinity chromatography, MutL and MutL-E32K both support formation of ternary complexes that also contain MutS and MutH or MutS and DNA helicase II. These findings imply that the MutL nucleotide binding center is required for mismatch repair and suggest that the dominant negative behavior of the MutL-E32K mutation is due to the formation of dead-end complexes in which the MutL-E32K protein is unable to transduce a signal from MutS that otherwise results in mismatch-dependent activation of the MutH d(GATC) endonuclease or the unwinding activity of helicase II.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 31, 2000

Volume

275

Issue

13

Start / End Page

9863 / 9869

Location

United States

Related Subject Headings

  • Protein Binding
  • MutL Proteins
  • Hydrolysis
  • Escherichia coli Proteins
  • Escherichia coli
  • DNA Repair
  • Biochemistry & Molecular Biology
  • Base Pair Mismatch
  • Bacterial Proteins
  • Adenosine Triphosphate
 

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Spampinato, C., & Modrich, P. (2000). The MutL ATPase is required for mismatch repair. J Biol Chem, 275(13), 9863–9869. https://doi.org/10.1074/jbc.275.13.9863
Spampinato, C., and P. Modrich. “The MutL ATPase is required for mismatch repair.J Biol Chem 275, no. 13 (March 31, 2000): 9863–69. https://doi.org/10.1074/jbc.275.13.9863.
Spampinato C, Modrich P. The MutL ATPase is required for mismatch repair. J Biol Chem. 2000 Mar 31;275(13):9863–9.
Spampinato, C., and P. Modrich. “The MutL ATPase is required for mismatch repair.J Biol Chem, vol. 275, no. 13, Mar. 2000, pp. 9863–69. Pubmed, doi:10.1074/jbc.275.13.9863.
Spampinato C, Modrich P. The MutL ATPase is required for mismatch repair. J Biol Chem. 2000 Mar 31;275(13):9863–9869.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 31, 2000

Volume

275

Issue

13

Start / End Page

9863 / 9869

Location

United States

Related Subject Headings

  • Protein Binding
  • MutL Proteins
  • Hydrolysis
  • Escherichia coli Proteins
  • Escherichia coli
  • DNA Repair
  • Biochemistry & Molecular Biology
  • Base Pair Mismatch
  • Bacterial Proteins
  • Adenosine Triphosphate