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TFB2M and POLRMT ar...
TFB2M and POLRMT are essential for mammalian mitochondrial DNA replication
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- Inatomi, Teppei (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Matsuda, Shigeru (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan; Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryocho, Aoba-ku, Miyagi, Sendai-shi, Japan
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- Ishiuchi, Takashi (author)
- Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Do, Yura (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Nakayama, Masunari (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Abe, Shusaku (author)
- Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Kasho, Kazutoshi (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Wanrooij, Sjoerd (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Nakada, Kazuto (author)
- Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki, Tsukuba-shi, Japan
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- Ichiyanagi, Kenji (author)
- Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Aichi, Nagoya-shi, Japan
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- Sasaki, Hiroyuki (author)
- Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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- Yasukawa, Takehiro (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan; Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
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- Kang, Dongchon (author)
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-shi, Japan
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier. - 0167-4889 .- 1879-2596. ; 1869:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Mitochondrial DNA
- Mitochondrial RNA polymerase
- Mitochondrial transcription factor
- Replication initiation
- Strand-asynchronous replication
- Strand-coupled replication
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Inatomi, Teppei
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Matsuda, Shigeru
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Ishiuchi, Takash ...
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Do, Yura
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Nakayama, Masuna ...
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Abe, Shusaku
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Kasho, Kazutoshi
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Wanrooij, Sjoerd
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Nakada, Kazuto
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Ichiyanagi, Kenj ...
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Sasaki, Hiroyuki
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Yasukawa, Takehi ...
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Kang, Dongchon
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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Biochimica et Bi ...
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Umeå University