Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Ctf18-RFC is an alternative PCNA loader which plays important but poorly understood roles in multiple DNA replication-associated processes. To fulfill its specialist roles, the Ctf18-RFC clamp loader contains a unique module in which the Dcc1-Ctf8 complex is bound to the C terminus of Ctf18 (the Ctf18-1-8 module). Here, we report the structural and functional characterization of the heterotetrameric complex formed between Ctf18-1-8 and a 63 kDa fragment of DNA polymerase ɛ. Our data reveal that Ctf18-1-8 binds stably to the polymerase and far from its other functional sites, suggesting that Ctf18-RFC could be associated with Pol ɛ throughout normal replication as the leading strand clamp loader. We also show that Pol ɛ and double-stranded DNA compete to bind the same winged-helix domain on Dcc1, with Pol ɛ being the preferred binding partner, thus suggesting that there are two alternative pathways to recruit Ctf18-RFC to sites of replication.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.str.2017.11.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular insights into the structure, function, and stability of the DNA polymerase processivity factor from Mycobacterium tuberculosis.
J Mol Biol
September 2025
Microbiology and Molecular Biology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal. Electronic address:
Emergence of drug resistance in Mycobacterium tuberculosis (Mtb) calls for newer drugs and drug targets. Essential proteins such as DNA polymerase (DNAP) processivity factor, also called sliding clamp (DnaN), are indispensable for bacterial survival, and are excellent drug targets. Here, we constructed a dnaN-conditional knockout in Mycobacterium smegmatis (MsmΔdnaN) and were able to successfully complement it with Mtb DnaN (DnaN).
View Article and Find Full Text PDFBackground: Sotrovimab is a neutralising monoclonal antibody targeting the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of sotrovimab in the RECOVERY trial, an investigator-initiated, individually randomised, controlled, open-label, adaptive platform trial testing treatments for patients admitted to hospital with COVID-19.
Methods: Patients admitted with COVID-19 pneumonia to 107 UK hospitals were randomly assigned (1:1) to either usual care alone or usual care plus a single 1 g infusion of sotrovimab, using web-based unstratified randomisation.
A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis.
bioRxiv
August 2025
Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY, USA.
The ring-shaped sliding clamp PCNA enables DNA polymerases to perform processive DNA synthesis during replication and repair. The loading of PCNA onto DNA is catalyzed by the ATPase clamp loader RFC. Using a single-molecule platform to visualize the dynamic interplay between PCNA and RFC on DNA, we unexpectedly discovered that RFC continues to associate with PCNA after loading, contrary to the conventional view.
View Article and Find Full Text PDFStructure of the human CTF18-RFC clamp loader bound to PCNA.
bioRxiv
July 2025
Bioscience Program, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
Sliding clamps like PCNA are crucial processivity factors for replicative polymerases, requiring specific clamp loaders for loading onto DNA. The human alternative clamp loader CTF18-RFC interacts with the leading strand polymerase Pol ε and loads PCNA onto primer/template DNA using its RFC pentameric module. Here, we provide a structural characterization of the human CTF18-RFC complex and its interaction with PCNA.
View Article and Find Full Text PDFDivide-and-conquer strategy for NMR studies of the E. coli γ-clamp loader complex.
J Biomol NMR
July 2025
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
The E. coli γ-clamp loader is a 200 kDa pentameric AAA + ATPase comprised of γ, δ and δ' subunits in a 3:1:1 ratio, which opens the ring shaped β-clamp homodimer and loads it onto DNA in a process essential for DNA replication. The clamp loading is initiated by ATP binding, which induces conformational changes in the clamp loader allowing it to bind and open the β-clamp.
View Article and Find Full Text PDF