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Biochemistry (Moscow)

, Volume 83, Issue 3, pp 281–293 | Cite as

Endonuclease Activity of MutL Protein of the Rhodobacter sphaeroides Mismatch Repair System

  • M. V. Monakhova
  • A. I. Penkina
  • A. V. Pavlova
  • A. M. Lyaschuk
  • V. V. Kucherenko
  • A. V. Alexeevski
  • V. G. Lunin
  • P. Friedhoff
  • G. Klug
  • T. S. Oretskaya
  • E. A. KubarevaEmail author
Article

Abstract

We have purified the MutL protein from Rhodobacter sphaeroides mismatch repair system (rsMutL) for the first time. rsMutL demonstrated endonuclease activity in vitro, as predicted by bioinformatics analysis. Based on the alignment of 1483 sequences of bacterial MutL homologs with presumed endonuclease activity, conserved functional motifs and amino acid residues in the rsMutL sequence were identified: five motifs comprising the catalytic site responsible for DNA cleavage were found in the C–terminal domain; seven conserved motifs involved in ATP binding and hydrolysis and specific to the GHKL family of ATPases were found in the N–terminal domain. rsMutL demonstrated the highest activity in the presence of Mn2+. The extent of plasmid DNA hydrolysis declined in the row Mn2+ > Co2+ > Mg2+ > Cd2+; Ni2+ and Ca2+ did not activate rsMutL. Divalent zinc ions inhibited rsMutL endonuclease activity in the presence of Mn2+ excess. ATP also suppressed plasmid DNA hydrolysis by rsMutL. Analysis of amino acid sequences and biochemical properties of five studied bacterial MutL homologs with endonuclease activity revealed that rsMutL resembles the MutL proteins from Neisseria gonorrhoeae and Pseudomonas aeruginosa.

Keywords

DNA repair mismatch MutL protein 

Abbreviations

a.a.

amino acid; bp

bp

base pair

DTT

1,4–dithiothreitol

ecMutL

MutL from Escherichia coli

GHKL

Gyrase Hsp90, Histidine Kinase, MutL family of ATPases

IPTG

isopropyl β–D–1–thiogalactopyranoside

LB

lysogeny broth

MMR

mismatch repair system

PMSF

phenylmethylsulfonyl fluoride

rsMutL

MutL from Rhodobacter sphaeroides

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • M. V. Monakhova
    • 1
  • A. I. Penkina
    • 2
  • A. V. Pavlova
    • 2
  • A. M. Lyaschuk
    • 3
  • V. V. Kucherenko
    • 4
  • A. V. Alexeevski
    • 1
    • 5
  • V. G. Lunin
    • 3
  • P. Friedhoff
    • 6
  • G. Klug
    • 7
  • T. S. Oretskaya
    • 2
  • E. A. Kubareva
    • 1
    Email author
  1. 1.Belozersky Institute of Physico–Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Chemistry DepartmentLomonosov Moscow State UniversityMoscowRussia
  3. 3.Gamaleya Research Institute of Epidemiology and MicrobiologyMoscowRussia
  4. 4.Bioengineering and Bioinformatics DepartmentLomonosov Moscow State UniversityMoscowRussia
  5. 5.Research Institute of System DevelopmentMoscowRussia
  6. 6.Institut für BiochemieJustus–Liebig–UniversitätGieβenGermany
  7. 7.Institut für Mikrobiologie und MolekularbiologieJustus–Liebig–UniversitätGieβenGermany

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