TFB2M and POLRMT are essential for mammalian mitochondrial DNA replication

Teppei Inatomi, Shigeru Matsuda, Takashi Ishiuchi, Yura Do, Masunari Nakayama, Shusaku Abe, Kazutoshi Kasho, Sjoerd Wanrooij, Kazuto Nakada, Kenji Ichiyanagi, Hiroyuki Sasaki, Takehiro Yasukawa, Dongchon Kang

研究成果: Contribution to journalArticle査読

抄録

Two classes of replication intermediates have been observed from mitochondrial DNA (mtDNA) in many mammalian tissue and cells with two-dimensional agarose gel electrophoresis. One is assigned to leading-strand synthesis in the absence of synchronous lagging-strand synthesis (strand-asynchronous replication), and the other has properties of coupled leading- and lagging-strand synthesis (strand-coupled replication). While strand-asynchronous replication is primed by long noncoding RNA synthesized from a defined transcription initiation site, little is known about the commencement of strand-coupled replication. To investigate it, we attempted to abolish strand-asynchronous replication in cultured human cybrid cells by knocking out the components of the transcription initiation complexes, mitochondrial transcription factor B2 (TFB2M/mtTFB2) and mitochondrial RNA polymerase (POLRMT/mtRNAP). Unexpectedly, removal of either protein resulted in complete mtDNA loss, demonstrating for the first time that TFB2M and POLRMT are indispensable for the maintenance of human mtDNA. Moreover, a lack of TFB2M could not be compensated for by mitochondrial transcription factor B1 (TFB1M/mtTFB1). These findings indicate that TFB2M and POLRMT are crucial for the priming of not only strand-asynchronous but also strand-coupled replication, providing deeper insights into the molecular basis of mtDNA replication initiation.

本文言語英語
論文番号119167
ジャーナルBiochimica et Biophysica Acta - Molecular Cell Research
1869
1
DOI
出版ステータス出版済み - 1 2022

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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