Catalytic loading
of PCNA is rate-limited by dissociation of RFC
from RPA-coated ssDNA. Each FRET trace represents the average of at
least eight shots. For comparison, all FRET traces are normalized
to the same starting value (at t = 0.005 s). (A)
Schematic representation of the experimental procedure for panel B.
(B) Cy5-PCNA (180 nM homotrimer) was preincubated with RFC (180 nM)
in the presence of ATP. This preformed RFC·Cy5-PCNA·ATP
complex was mixed with Cy3P/BioT DNA (200 nM), RPA (285 nM), and ATP
in a stopped-flow instrument, and the FRET signal was followed. The
loading trace was fit to a double-exponential equation, and the kinetic
values are reported. (C) Schematic representation of the experimental
procedure for panel D. (D) Unlabeled P/BioT DNA (200 nM) was preincubated
with RPA (285 nM), Cy5-PCNA (180 nM homotrimer), RFC (180 nM), and
ATP. This solution was then mixed with Cy3P/BioT DNA (200 nM), RPA
(285 nM), and ATP in a stopped-flow instrument, and the FRET signal
was followed. The loading trace was fit to a single-exponential equation,
and the rate constant is reported. (E) Schematic representation of
the experimental procedure for panel F. (F) The experiments depicted
in panels C and D were repeated except RPA (285 nM), Cy5-PCNA (180
nM homotrimer), RFC (180 nM), and ATP were preincubated with unlabeled
P/T DNA (200 nM). The loading trace was fit to a single-exponential
equation, and the kinetic values are reported.