The Mcm4/Mcm7 assembly unwinds DNA substrates with 3′-to
5′-polarity in a manner consistent with a steric exclusion
mechanism. A, equimolar mixture of Mcm4/Mcm7 was incubated at 37
°C with various DNA substrates for the time points indicated, and
unwinding was monitored by native gel electrophoresis as described under
“Experimental Procedures.” The DNA oligonucleotides used in these
experiments are detailed in supplemental Table 1. The time course data for
each DNA substrate were fit with a logarithmic or linear equation. Each
substrate is composed of identical dsDNA sequence bearing the following
extensions: a 3′-60(dT)-ssDNA extension and a
5′-biotin-streptavidin (filled squares), a 3′-60(dT)
ssDNA extension and a 5′-60(dT) ssDNA extension (open squares),
a 5′-60(dT) ssDNA extension and a 3′-biotin-streptavidin (open
diamonds), a 5′-60(dT) extension (filled triangles), and a
3′-60(dT) ssDNA extension (open circles). B, model of
how Mcm4/Mcm6/Mcm7 unwinds a tandem duplex DNA substrate by a steric exclusion
mechanism (35). The bottom
strand is continuous, and the top strand bears a nick, creating
two DNA duplexes in tandem. The left duplex bears a 3′-60(dT)
ssDNA extension, and the right duplex bears a 5′-60(dT) ssDNA
extension. Mcm4/Mcm6/Mcm7 unwinds only the right strand of this tandem duplex
substrate. C, equimolar mixture of Mcm4/Mcm7 was incubated with a
tandem duplex substrate and ATP at 37 °C for the time points indicated
(lanes 3-6). The left duplex bears a 3′-60(dT) ssDNA
extension, and the right duplex bears a 5′-60(dT) ssDNA
extension. UvrD was used as a SF1 helicase family control (lane 2),
and a no protein control is also shown (lane 1). D, data
from experiments similar to C were quantified and plotted as a
function of time. Data are shown for the tandem duplex substrate bearing a
3′-ssDNA extension (diamonds) and for a similar substrate that
lacks the 3′-ssDNA extension (squares). For each DNA product,
the time point data were fit to a linear equation. E, this experiment
is similar to C, except a different strand is radiolabeled.
F, data from experiments similar to E were quantified and
plotted as a function of time for each DNA product.