Multiple competition reactions for RPA order the assembly of the DNA polymerase delta holoenzyme.
Processive extension of DNA in eukaryotes requires three factors to coordinate their actions. First, DNA polymerase alpha-primase synthesizes the primed site. Then replication factor C loads a proliferating cell nuclear antigen (PCNA) clamp onto the primer. Following this, DNA polymerase delta assembles with PCNA for processive extension. This report shows that these proteins each bind the primed site tightly and trade places in a highly coordinated fashion such that the primer terminus is never left free of protein. Replication protein A (RPA), the single-stranded DNA-binding protein, forms a common touchpoint for each of these proteins and they compete with one another for it. Thus these protein exchanges are driven by competition-based protein switches in which two proteins vie for contact with RPA.
Yuzhakov
A
A
The Rockefeller University, New York, New York 10021, USA.
Kelman
Z
Z
Hurwitz
J
J
O'Donnell
M
M
D001667:Binding, Competitive; D004258:DNA Polymerase III / Q000378:metabolism*; D019915:DNA Primase / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli; D018398:Homeodomain Proteins; D006801:Humans; D007700:Kinetics; D015778:Minor Histocompatibility Antigens; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2; D051716:Replication Protein A; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
C096816:BCL2-related protein A1; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C497167:RPA1 protein, human; D051716:Replication Protein A; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D019915:DNA Primase; D004258:DNA Polymerase III; D051818:Replication Protein C