The human MSH5 (MutSHomolog 5) protein localizes to mitochondria and protects the mitochondrial genome from oxidative damage

Mitochondrion. 2012 Nov;12(6):654-65. doi: 10.1016/j.mito.2012.07.111. Epub 2012 Aug 11.

Abstract

MutS homologs play a central role in maintaining genetic stability. We show that MSH5 (MutSHomolog 5) is localized into the mitochondria of germ and somatic cells. This protein binds to mtDNA and interacts with the Twinkle helicase and the DNA polymerase gamma. hMSH5 stimulates mtDNA repair in response to DNA damage induced by oxidative stress. Furthermore, we observed a subsarcolemmal accumulation of hMSH5 in COX negative muscle fibers of patients presenting a mitochondrial myopathy. We report a novel localization for hMSH5 suggesting that this protein may have functions other than those known in meiotic recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / analysis*
  • Cell Line
  • DNA Damage*
  • DNA Repair
  • DNA, Mitochondrial / drug effects*
  • DNA, Mitochondrial / metabolism
  • Humans
  • Mitochondria / chemistry*
  • Oxidants / toxicity*
  • Oxidative Stress
  • Protein Binding

Substances

  • Cell Cycle Proteins
  • DNA, Mitochondrial
  • MSH5 protein, human
  • Oxidants