The human MSH5 (MutSHomolog 5) protein localizes to mitochondria and protects the mitochondrial genome from oxidative damage.
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.
IRCAN, CNRS UMR 7284/Inserm U1081/UNS, Faculté de Médecine, 06107 Nice Cedex 2, France.
Sylvie
S
Bannwarth
Alexia
A
Figueroa
Konstantina
K
Fragaki
Laurie
L
Destroismaisons
Sandra
S
Lacas-Gervais
Françoise
F
Lespinasse
Fanny
F
Vandenbos
Ludivine A
LA
Pradelli
Jean-Ehrland
JE
Ricci
Agnès
A
Rötig
Jean-François
JF
Michiels
Christine
C
Vande Velde
Véronique
V
Paquis-Flucklinger
D018797:Cell Cycle Proteins / Q000032:analysis*; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000737:chemistry*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D011485:Protein Binding
D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; C118481:MSH5 protein, human; D016877:Oxidants