NDLI: The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA

Content Provider	PubMed Central
Author	Hyvärinen, Anne K. Pohjoismäki, Jaakko L. O. Reyes, Aurelio Wanrooij, Sjoerd Yasukawa, Takehiro Karhunen, Pekka J. Spelbrink, Johannes N. Holt, Ian J. Jacobs, Howard T.
Copyright Year	2007
Abstract	The mammalian mitochondrial transcription termination factor mTERF binds with high affinity to a site within the tRNALeu(UUR) gene and regulates the amount of read through transcription from the ribosomal DNA into the remaining genes of the major coding strand of mitochondrial DNA (mtDNA). Electrophoretic mobility shift assays (EMSA) and SELEX, using mitochondrial protein extracts from cells induced to overexpress mTERF, revealed novel, weaker mTERF-binding sites, clustered in several regions of mtDNA, notably in the major non-coding region (NCR). Such binding in vivo was supported by mtDNA immunoprecipitation. Two-dimensional neutral agarose gel electrophoresis (2DNAGE) and 5′ end mapping by ligation-mediated PCR (LM-PCR) identified the region of the canonical mTERF-binding site as a replication pause site. The strength of pausing was modulated by the expression level of mTERF. mTERF overexpression also affected replication pausing in other regions of the genome in which mTERF binding was found. These results indicate a role for TERF in mtDNA replication, in addition to its role in transcription. We suggest that mTERF could provide a system for coordinating the passage of replication and transcription complexes, analogous with replication pause-region binding proteins in other systems, whose main role is to safeguard the integrity of the genome whilst facilitating its efficient expression.
Related Links	http://dx.doi.org/10.1093/nar/gkm676
Ending Page	6474
Page Count	17
Starting Page	6458
File Format	PDF
ISSN	03051048
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	19
Volume Number	35
Language	English
Publisher	Oxford University Press
Publisher Date	2007-10-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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