TY - JOUR
T1 - Pumps, paradoxes and ploughshares
T2 - Mechanism of the MCM2-7 DNA helicase
AU - Takahashi, Tatsuro S.
AU - Wigley, Dale B.
AU - Walter, Johannes C.
N1 - Funding Information:
We thank Dave Gilbert, Anindya Dutta and Marcin Pacek for helpful discussions. We thank the Keystone Symposium and Resort for providing the hot tub in which some of the ideas presented were hatched. J.C.W. is supported by NIH grant GM62267.
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=22744445013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22744445013&partnerID=8YFLogxK
U2 - 10.1016/j.tibs.2005.06.007
DO - 10.1016/j.tibs.2005.06.007
M3 - Article
C2 - 16002295
AN - SCOPUS:22744445013
SN - 0376-5067
VL - 30
SP - 437
EP - 444
JO - Trends in Biochemical Sciences
JF - Trends in Biochemical Sciences
IS - 8
ER -