Mitochondrial transcription termination factor 1 directs polar replication fork pausing

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Shi , Y , Posse , V , Zhu , X , Hyvärinen , A K , Jacobs , H T , Falkenberg , M & Gustafsson , C M 2016 , ' Mitochondrial transcription termination factor 1 directs polar replication fork pausing ' , Nucleic Acids Research , vol. 44 , no. 12 , pp. 5732-5742 . https://doi.org/10.1093/nar/gkw302

Title: Mitochondrial transcription termination factor 1 directs polar replication fork pausing
Author: Shi, Yonghong; Posse, Viktor; Zhu, Xuefeng; Hyvärinen, Anne K.; Jacobs, Howard T.; Falkenberg, Maria; Gustafsson, Claes M.
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2016-07-08
Language: eng
Number of pages: 11
Belongs to series: Nucleic Acids Research
ISSN: 0305-1048
URI: http://hdl.handle.net/10138/208454
Abstract: During replication of nuclear ribosomal DNA (rDNA), clashes with the transcription apparatus can cause replication fork collapse and genomic instability. To avoid this problem, a replication fork barrier protein is situated downstream of rDNA, there preventing replication in the direction opposite rDNA transcription. A potential candidate for a similar function in mitochondria is the mitochondrial transcription termination factor 1 (MTERF1, also denoted mTERF), which binds to a sequence just downstream of the ribosomal transcription unit. Previous studies have shown that MTERF1 prevents antisense transcription over the ribosomal RNA genes, a process which we here show to be independent of the transcription elongation factor TEFM. Importantly, we now demonstrate that MTERF1 arrests mitochondrial DNA (mtDNA) replication with distinct polarity. The effect is explained by the ability of MTERF1 to act as a directional contrahelicase, blocking mtDNA unwinding by the mitochondrial helicase TWINKLE. This conclusion is also supported by in vivo evidence that MTERF1 stimulates TWINKLE pausing. We conclude that MTERF1 can direct polar replication fork arrest in mammalian mitochondria.
Subject: DNA-POLYMERASE-GAMMA
IN-VITRO
BINDING PROTEIN
RNA-POLYMERASE
RIBOSOMAL-RNA
FACTOR MTERF
LAGGING-STRAND
HUMAN MTDNA
TWINKLE
CELLS
1182 Biochemistry, cell and molecular biology
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