Mitochondrial DNA replication in human T lymphocytes is regulated primarily at the H-strand termination site

Yoichiro Kai, Kenichi Miyako, Tsuyoshi Muta, Shuyo Umeda, Takashi Irie, Naotaka Hamasaki, Koichiro Takeshige, Dongchon Kang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The most unique feature in the replication of mitochondrial DNA (mtDNA) is that most of the newly synthesized heavy strands (H-strands) terminate prematurely, resulting in the formation of displacement loop (D-loop) strands. Only the H-strand which proceeds past the termination site is a true nascent H-strand leading to the overall replication on a circular mtDNA molecule. The physiological significance of the D-loop formation has long been unclear. To examine the role of premature termination in mtDNA replication, we therefore developed a method for selectively measuring both the total amount of nascent H-strands and the amount of true nascent H-strands using ligation-mediated polymerase chain reaction, which, for the first time, enabled us to estimate the frequency of premature termination. The stimulation of cell proliferation with interleukin 2 and phytohemagglutinin in human peripheral T lymphocytes caused an increase in the net replication rate of mtDNA. In stimulated cells, in comparison to resting ones, the amount of true nascent H-strands increased approx. 2.6-fold while the total amount of nascent H-strands remained unchanged, indicating that premature termination decreased while the initiation of replication remained the same. Our findings thus demonstrate the first clear example that premature termination plays a primary role in the up-regulation of the net rate of mtDNA replication in human cells. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1446
Issue number1-2
DOIs
Publication statusPublished - Jul 7 1999

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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