Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair

Alfredo De Biasio, Alain Ibáñez De Opakua, Gulnahar B. Mortuza, Rafael Molina, Tiago N. Cordeiro, Francisco Castillo, Maider Villate, Nekane Merino, Sandra Delgado, David Gil-Cartón, Irene Luque, Tammo Diercks, Pau Bernadó, Guillermo Montoya, Francisco J. Blanco

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


The intrinsically disordered protein p15PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15PAF-PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP-box) of p15PAF tightly bound to the front-face of PCNA. In contrast to other PCNA-interacting proteins, p15PAF also contacts the inside of, and passes through, the PCNA ring. The disordered p15PAF termini emerge at opposite faces of the ring, but remain protected from 20S proteasomal degradation. Both free and PCNA-bound p15PAF binds DNA mainly through its histone-like N-terminal tail, while PCNA does not, and a model of the ternary complex with DNA inside the PCNA ring is consistent with electron micrographs. We propose that p15PAF acts as a flexible drag that regulates PCNA sliding along the DNA and facilitates the switch from replicative to translesion synthesis polymerase binding.
Original languageEnglish (US)
JournalNature Communications
StatePublished - Mar 12 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Chemistry
  • General Physics and Astronomy


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