DNA translocation mechanism of the MCM complex and implications for replication initiation
Journal Article
·
· Nature Communications
- St. Jude's Children's Research Hospital, Memphis, TN (United States); DOE/OSTI
- St. Jude's Children's Research Hospital, Memphis, TN (United States); Incyte Research Institute, Wilmington, DE (United States)
- St. Jude's Children's Research Hospital, Memphis, TN (United States)
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.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- American Lebanese Syrian Associated Charities (ALSAC); Comprehensive Cancer Center Support; National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 1557308
- Journal Information:
- Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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