Replisome assembly reveals the basis for asymmetric function in leading and lagging strand replication.
The E. coli replicase, DNA polymerase III holoenzyme, contains two polymerases for replication of duplex DNA. The DNA strands are antiparallel requiring different modes of replicating the two strands: one is continuous (leading) while the other is discontinuous (lagging). The two polymerases within holoenzyme are generally thought to have asymmetric functions for replication of these two strands. This report finds that the two polymerases have equal properties, both are capable of replicating the more difficult lagging strand. Asymmetric action is, however, imposed by the helicase that encircles the lagging strand. The helicase contact defines the leading polymerase constraining it to a subset of actions, while leaving the other to cycle on the lagging strand. The symmetric actions of the two polymerases free holoenzyme to assemble into the replisome in either orientation without concern for a correct match to one or the other strand.
Yuzhakov
A
A
Microbiology Department, Howard Hughes Medical Institute, Cornell University Medical College, New York 10021, USA.
Turner
J
J
O'Donnell
M
M
D001426:Bacterial Proteins / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004258:DNA Polymerase III / Q000737:chemistry / Q000378:metabolism; D019915:DNA Primase; D004261:DNA Replication / Q000502:physiology*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism; D053488:DnaB Helicases; D004926:Escherichia coli / Q000378:metabolism; D011487:Protein Conformation; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D012093:Replicon
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D019915:DNA Primase; C023140:DNA replicase; D012316:RNA Nucleotidyltransferases; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; D004265:DNA Helicases; D053488:DnaB Helicases