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

The intrinsically disordered protein p15 PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15 PAF –PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP-box)...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2015-03, Vol.6 (1), p.6439, Article 6439
Main Authors: De Biasio, Alfredo, de Opakua, Alain Ibáñez, Mortuza, Gulnahar B., Molina, Rafael, Cordeiro, Tiago N., Castillo, Francisco, Villate, Maider, Merino, Nekane, Delgado, Sandra, Gil-Cartón, David, Luque, Irene, Diercks, Tammo, Bernadó, Pau, Montoya, Guillermo, Blanco, Francisco J.
Format: Article
Language:English
Subjects:
101/28
101/6
119/118
140/131
631/337/1427
631/337/151/2354
631/45/470
631/57
82/83
Humanities and Social Sciences
multidisciplinary
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The intrinsically disordered protein p15 PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present the structure of the human p15 PAF –PCNA complex. Crystallography and NMR show the central PCNA-interacting protein motif (PIP-box) of p15 PAF tightly bound to the front-face of PCNA. In contrast to other PCNA-interacting proteins, p15 PAF also contacts the inside of, and passes through, the PCNA ring. The disordered p15 PAF termini emerge at opposite faces of the ring, but remain protected from 20S proteasomal degradation. Both free and PCNA-bound p15 PAF 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 p15 PAF acts as a flexible drag that regulates PCNA sliding along the DNA and facilitates the switch from replicative to translesion synthesis polymerase binding. p15PAF regulates DNA replication and repair via interactions with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp. Here the authors present multi-faceted structural analyses of the p15-PCNA-DNA complex that suggests p15 regulates the sliding of PCNA along DNA during replication.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms7439