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Structure of p15(PAF)-PCNA complex and implications for clamp sliding during DNA replication and repair

Alfredo De Biasio1, Alain Ibáñez de Opakua1, Gulnahar B Mortuza2

  • 1Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia Edificio 800, 48160 Derio, Spain.

Nature Communications
|March 13, 2015
PubMed

Insights

The intrinsically disordered protein p15(PAF) binds the PCNA sliding clamp, uniquely passing through its ring. This interaction regulates DNA replication and repair processes.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • The intrinsically disordered protein p15(PAF) plays a crucial role in DNA replication and repair.
  • p15(PAF) interacts with the proliferating cell nuclear antigen (PCNA) sliding clamp, a key component in these processes.

Purpose of the Study:

  • To elucidate the structural basis of the p15(PAF)-PCNA complex formation.
  • To understand the functional implications of this interaction in DNA metabolism.

Main Methods:

  • X-ray crystallography
  • Nuclear Magnetic Resonance (NMR) spectroscopy
  • Biophysical assays
  • Computational modeling

Main Results:

  • The structure reveals the PCNA-interacting protein motif (PIP-box) of p15(PAF) binding to the PCNA front-face.
  • p15(PAF) uniquely passes through the PCNA ring, with termini emerging on opposite sides.
  • p15(PAF) binds DNA via its N-terminal tail, independent of PCNA.
  • The complex is protected from proteasomal degradation.

Conclusions:

  • p15(PAF) acts as a flexible regulator of PCNA sliding along DNA.
  • This interaction facilitates the transition between replicative and translesion synthesis polymerases.
  • The unique binding mode suggests a novel mechanism for controlling DNA processing.

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