Mechanism of transcription initiation and primer generation at the mitochondrial replication origin OriL
| Autor: | Michael Anikin, Azadeh Sarfallah, Angelica Zamudio-Ochoa, Dmitry Temiakov |
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| Rok vydání: | 2021 |
| Předmět: |
DNA Replication
Models Molecular Mitochondrial DNA POLRMT Molecular Conformation Replication Origin Biology DNA Mitochondrial Primosome General Biochemistry Genetics and Molecular Biology Mitochondrial Proteins Structure-Activity Relationship Transcription (biology) Molecular Biology Transcription Initiation Genetic Polymerase Base Sequence General Immunology and Microbiology Mechanism (biology) General Neuroscience Articles Mitochondria Cell biology DNA-Binding Proteins biology.protein Nucleic Acid Conformation RNA Replisome Primer (molecular biology) |
| Zdroj: | EMBO J |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.2021107988 |
| Popis: | The intricate process of human mtDNA replication requires the coordinated action of both transcription and replication machineries. Transcription and replication events at the lagging strand of mtDNA prompt the formation of a stem-loop structure (OriL) and the synthesis of a ∼25 nt RNA primer by mitochondrial RNA polymerase (mtRNAP). The mechanisms by which mtRNAP recognizes OriL, initiates transcription, and transfers the primer to the replisome are poorly understood. We found that transcription initiation at OriL involves slippage of the nascent transcript. The transcript slippage is essential for initiation complex stability and its ability to translocate the mitochondrial DNA polymerase gamma, PolG, which pre-binds to OriL, downstream of the replication origin thus allowing for the primer synthesis. Our data suggest the primosome assembly at OriL-a complex of mtRNAP and PolG-can efficiently generate the primer, transfer it to the replisome, and protect it from degradation by mitochondrial endonucleases. |
| Databáze: | OpenAIRE |
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