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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
Published on: March 12, 2017
Mitochondrial transcription termination factor 1 directs polar replication fork pausing
Yonghong Shi1, Viktor Posse2, Xuefeng Zhu1
1Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
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.
Insights
Mitochondrial transcription termination factor 1 (MTERF1) acts as a directional contrahelicase, blocking mitochondrial DNA replication. This protein prevents replication fork collapse, ensuring genomic stability in mammalian mitochondria.
Area of Science:
- Mitochondrial biology
- Molecular genetics
- Genomics
Background:
- Nuclear ribosomal DNA (rDNA) replication faces challenges from transcription machinery, necessitating replication fork barriers.
- Mitochondrial transcription termination factor 1 (MTERF1) is a candidate protein for a similar role in mitochondria, located downstream of the ribosomal transcription unit.
Purpose of the Study:
- To investigate the role of MTERF1 in mitochondrial DNA (mtDNA) replication.
- To determine if MTERF1 functions as a replication fork barrier in mammalian mitochondria.
Main Methods:
- Assessed MTERF1's effect on mtDNA replication polarity.
- Investigated MTERF1's interaction with the mitochondrial helicase TWINKLE.
- Utilized in vivo evidence to support MTERF1's role in TWINKLE pausing.
Main Results:
- MTERF1 arrests mtDNA replication with a distinct polarity.
- MTERF1 functions as a directional contrahelicase, inhibiting mtDNA unwinding by TWINKLE.
- In vivo data shows MTERF1 enhances TWINKLE pausing.
Conclusions:
- MTERF1 directs polar replication fork arrest in mammalian mitochondria.
- This mechanism prevents replication conflicts and maintains mitochondrial genome stability.
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