1-Methyl-4-phenylpyridinium ion, a toxin that can cause parkinsonism, alters branched structures of DNA.
During replication, human mitochondrial DNA (mtDNA) takes on a triple-stranded structure known as a D-loop, which is implicated in replication and transcription. 1-Methyl-4-phenylpyridinium ion (MPP+), a toxin inducing parkinsonism, inhibits mtDNA replication, possibly by resolving the D-loops. For initiation of mtDNA replication, mitochondria are thought to have another triple-stranded structure, an R-loop. The R-loop, which is resolved by a bacterial junction-specific helicase, RecG, is also resolved by MPP+. Because mitochondrial D-loops are likewise resolved by RecG, the D- and R-loops may share a similar branched structure. MPP+ resolves cruciform DNA in supercoiled DNA. MPP+ converts a stacked conformation to an extended conformation in a synthetic Holliday junction. This conversion is reversed by 1 mM Mg(2+), as is the resolution of the D-loops or cruciform DNA. These observations suggest that the junction structure of mitochondrial D- and R-loops is affected by MPP+.
Iwaasa
Mitsutoshi
M
Department of Neurosurgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Umeda
Shuyo
S
Ohsato
Takashi
T
Takamatsu
Chihiro
C
Fukuoh
Atushi
A
Iwasaki
Hiroshi
H
Shinagawa
Hideo
H
Hamasaki
Naotaka
N
Kang
Dongchon
D
D015655:1-Methyl-4-phenylpyridinium / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology; D004265:DNA Helicases / Q000737:chemistry / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000187:drug effects*; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000139:chemically induced
D001426:Bacterial Proteins; D004272:DNA, Mitochondrial; D004278:DNA, Superhelical; D029968:Escherichia coli Proteins; D007364:Intercalating Agents; C071446:RecG protein, E coli; D004265:DNA Helicases; D008274:Magnesium; D015655:1-Methyl-4-phenylpyridinium