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DNA-dependent activation of the hMutSalpha ATPase.

Publication ,  Journal Article
Blackwell, LJ; Bjornson, KP; Modrich, P
Published in: J Biol Chem
November 27, 1998

ATP hydrolysis by MutS homologs is required for function of these proteins in mismatch repair. However, the function of ATP hydrolysis in the repair reaction is controversial. In this paper we describe a steady-state kinetic analysis of the DNA-activated ATPase of human MutSalpha. Comparison of salt concentration effects on mismatch repair and mismatch-provoked excision in HeLa nuclear extracts with salt effects on the DNA-activated ATPase suggests that ATP hydrolysis by MutSalpha is involved in the rate determining step in the repair pathway. While the ATPase is activated by homoduplex and heteroduplex DNA, the half-maximal concentration for activation by heteroduplex DNA is significantly lower under physiological salt concentrations. Furthermore, at optimal salt concentration, heteroduplex DNA increases the kcat for ATP hydrolysis to a greater extent than does homoduplex DNA. We also demonstrate that the degree of ATPase activation is dependent on DNA chain length, with the kcat for hydrolysis increasing significantly with chain length of the DNA cofactor. These results are discussed in terms of the translocation (Allen, D. J., Makhov, A., Grilley, M., Taylor, J., Thresher, R., Modrich, P., and Griffith, J. D. (1997) EMBO J. 16, 4467-4476) and the molecular switch (Gradia, S., Acharya, S., and Fishel, R. (1997) Cell 91, 995-1005) models that invoke distinct roles for ATP hydrolysis in MutS homolog function.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 27, 1998

Volume

273

Issue

48

Start / End Page

32049 / 32054

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Potassium Chloride
  • Oligodeoxyribonucleotides
  • Nucleic Acid Heteroduplexes
  • MutS Homolog 3 Protein
  • Multienzyme Complexes
  • Multidrug Resistance-Associated Proteins
  • Molecular Sequence Data
  • Kinetics
  • Humans
 

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Blackwell, L. J., Bjornson, K. P., & Modrich, P. (1998). DNA-dependent activation of the hMutSalpha ATPase. J Biol Chem, 273(48), 32049–32054. https://doi.org/10.1074/jbc.273.48.32049
Blackwell, L. J., K. P. Bjornson, and P. Modrich. “DNA-dependent activation of the hMutSalpha ATPase.J Biol Chem 273, no. 48 (November 27, 1998): 32049–54. https://doi.org/10.1074/jbc.273.48.32049.
Blackwell LJ, Bjornson KP, Modrich P. DNA-dependent activation of the hMutSalpha ATPase. J Biol Chem. 1998 Nov 27;273(48):32049–54.
Blackwell, L. J., et al. “DNA-dependent activation of the hMutSalpha ATPase.J Biol Chem, vol. 273, no. 48, Nov. 1998, pp. 32049–54. Pubmed, doi:10.1074/jbc.273.48.32049.
Blackwell LJ, Bjornson KP, Modrich P. DNA-dependent activation of the hMutSalpha ATPase. J Biol Chem. 1998 Nov 27;273(48):32049–32054.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 27, 1998

Volume

273

Issue

48

Start / End Page

32049 / 32054

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Potassium Chloride
  • Oligodeoxyribonucleotides
  • Nucleic Acid Heteroduplexes
  • MutS Homolog 3 Protein
  • Multienzyme Complexes
  • Multidrug Resistance-Associated Proteins
  • Molecular Sequence Data
  • Kinetics
  • Humans