Sliding clamps encircle and slide along duplex DNA, acting as a mobile platform to localize DNA polymerase or other binding partners, to promote processive DNA synthesis and regulate the activities of many proteins involved in DNA repair. Proliferating cell nuclear antigen (PCNA) is the eukaryotic sliding clamp that functions as a hub protein and plays critical roles in many essential processes, including DNA replication, cell cycle control, nucleotide excision repair, break-induced replication, mismatch repair, and chromatin assembly. Loading of a sliding clamp onto DNA is accomplished by clamp loaders, which belong to the AAA+ family (ATPases associated with various cellular activities). Pioneering studies on crystal structures of clamp loaders of eukaryotes, archaea, bacteria, and the T4 bacteriophage, revealed key insights into the clamp loading mechanism of clamp loaders. The CTF18-RFC complex is an alternative clamp loader found recently to bind the leading strand DNA polymerase ε and load PCNA onto leading strand DNA. CTF18-RFC is a heptamer with two additional non-ATPase subunits DCC1 and CTF8. In vitro assays have shown that Ctf18-RFC only loads PCNA onto a 3′-recessed DNA, like RFC, but the loading activity is lower than that of RFC. Here you can see a cryoEM model of the human CTF18-RFC-PCNA-DNA ternary complex with narrow PCNA opening state, as part of a complete study published in PNAS by He and coworkers (PDB code: 8UMV)

#molecularart #DNA #polymerase #clamp #loader #complex #CTF18 #cryoem

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint