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Göteborgs universitets publikationer

Mitochondrial transcription termination factor 1 directs polar replication fork pausing

Författare och institution:
Yonghong Shi (Institutionen för biomedicin); Viktor Posse (Institutionen för biomedicin); Xuefeng Zhu (Institutionen för biomedicin); A. K. Hyvarinen (-); H. T. Jacobs (-); Maria Falkenberg (Institutionen för biomedicin); Claes M Gustafsson (Institutionen för biomedicin)
Publicerad i:
Nucleic Acids Research, 44 ( 12 ) s. 5732-5742
Artikel, refereegranskad vetenskaplig
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinsk bioteknologi
dna-polymerase-gamma, in-vitro, binding protein, rna-polymerase, ribosomal-rna, factor mterf, lagging-strand, human mtdna, twinkle, cells, Biochemistry & Molecular Biology
The enzymatic machinery of human mitochondrial dna maintenance (REPMIT) (EC/FP7/261248)
Postens nummer:
Posten skapad:
2016-09-26 13:24
Posten ändrad:
2016-10-14 07:38

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