DNA translocation mechanism of the MCM complex and implications for replication initiation
| Autor: | Eric J. Enemark, Martin Meagher, Leslie B Epling |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
Science General Physics and Astronomy Chromosomal translocation Random hexamer Crystallography X-Ray General Biochemistry Genetics and Molecular Biology Translocation Genetic Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Minichromosome maintenance MCM complex Nucleotide lcsh:Science 030304 developmental biology X-ray crystallography chemistry.chemical_classification Adenosine Triphosphatases 0303 health sciences Multidisciplinary Minichromosome Maintenance Proteins Chemistry DNA replication General Chemistry enzymes and coenzymes (carbohydrates) DNA Archaeal Replication Initiation Biophysics Sulfolobus solfataricus lcsh:Q Replisome 030217 neurology & neurosurgery DNA |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The DNA translocation activity of the minichromosome maintenance (MCM) complex powers DNA strand separation of the replication forks of eukaryotes and archaea. Here we illustrate an atomic level mechanism for this activity with a crystal structure of an archaeal MCM hexamer bound to single-stranded DNA and nucleotide cofactors. Sequence conservation indicates this rotary mechanism is fully possible for all eukaryotes and archaea. The structure definitively demonstrates the ring orients during translocation with the N-terminal domain leading, indicating that the translocation activity could also provide the physical basis of replication initiation where a double-hexamer idly encircling double-stranded DNA transforms to single-hexamers that encircle only one strand. In this mechanism, each strand binds to the N-terminal tier of one hexamer and the AAA+ tier of the other hexamer such that one ring pulls on the other, aligning equivalent interfaces to enable each hexamer to pull its translocation strand outside of the opposing hexamer. Eukaryotes and archaea use a heximeric ring-shaped MCM helicase to unwind the DNA template during replication. Here the authors present a crystal structure of the MCM complex from archaeon S. solfataricus bound to single-stranded DNA, and to a combination of ADP, and ATP-mimic, ADP-BeF3. |
| Databáze: | OpenAIRE |
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