What the study found
The human CTF18–RFC clamp loader has distinctive structural features, including a flexible regulatory module and an autoinhibited RFC module bound to PCNA. The study also identifies a novel β-hairpin in the large subunit that helps connect the complex to PCNA and the RFC5 subunit.
Why the authors say this matters
The authors conclude that these structural features provide insight into how CTF18–RFC loads PCNA and how it may stimulate leading-strand synthesis by Pol ε, a leading-strand DNA polymerase.
What the researchers tested
The researchers used cryo-electron microscopy (cryo-EM) to characterize the human CTF18–RFC complex and its interaction with PCNA. They examined the structure of the complex and tested the effect of deleting a β-hairpin on complex stability, clamp loading, and primer synthesis.
What worked and what didn't
Cryo-EM data supported that the Ctf8 and Dcc1 subunits are flexibly tethered to the RFC module. A 2.9 Å cryo-EM structure showed the RFC module bound to PCNA in an autoinhibited conformation similar to canonical RFC, and deletion of the β-hairpin impaired complex stability, slowed clamp loading, and decreased the rate of primer synthesis by Pol ε.
What to keep in mind
The abstract does not describe broader biological limits beyond the structural and functional observations reported here. It also does not provide details on experiments outside the CTF18–RFC/PCNA system.
Key points
- CTF18–RFC was found to have a flexible regulatory module made of Ctf8 and Dcc1.
- A 2.9 Å cryo-EM structure showed the RFC module bound to PCNA in an autoinhibited state.
- The large subunit of CTF18–RFC uses an atypical low-affinity PIP box and a novel β-hairpin to engage PCNA and RFC5.
- Deleting the β-hairpin weakened the CTF18–RFC–PCNA complex and slowed clamp loading.
- β-hairpin deletion also reduced the rate of primer synthesis by Pol ε.
Disclosure
- Research title:
- CTF18-RFC structure reveals how it binds PCNA
- Authors:
- Giuseppina R. Briola, Mohammad Tehseen, Amani Al-Amodi, Grace Young, Ammar Usman Danazumi, Phong Quoc Nguyen, Christos G. Savva, Mark Hedglin, Samir M Hamdan, Alfredo De Biasio
- Institutions:
- King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, King Abdullah University of Science and Technology, Pennsylvania State University, Pennsylvania State University
- Publication date:
- 2026-02-23
- OpenAlex record:
- View
- Image credit:
- Photo by Nicola Narracci on Pexels
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