Pumps, paradoxes and ploughshares: mechanism of the MCM2-7 DNA helicase.
In eukaryotes, numerous lines of evidence have coalesced into a convincing case that the MCM2-7 complex - a heterohexameric ATPase - is the replicative DNA helicase. However, almost nothing is known about how this enzyme functions in a cellular context. Some models for the mechanism of the MCM2-7 helicase envision that it translocates along single-stranded DNA (ssDNA), whereas, more recently, it is has been suggested that it pumps double-stranded DNA (dsDNA) through its central channel. In particular, one model in which a double hexamer of MCM2-7 pumps dsDNA towards the hexamer interface and extrudes ssDNA laterally as a result of torsional strain is gaining popularity. Here, we discuss existing models and propose a new variation in which a single hexamer is the functional unit of the helicase. Duplex DNA is pumped into MCM2-7 and, as it emerges from the complex, a rigid protein that we term the 'ploughshare' splits the duplex.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Tatsuro S
TS
Takahashi
Dale B
DB
Wigley
Johannes C
JC
Walter
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D004247:DNA; D004265:DNA Helicases