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

doi:10.1038/ncomms7439

Structure of p15^PAF-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

Protein Structure and Function Program

43 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	6439
Tidsskrift	Nature Communications
Vol/bind	6
Sider (fra-til)	1-12
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms7439
Status	Udgivet - 12 mar. 2015

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10.1038/ncomms7439

Citationsformater

De Biasio, A., de Opakua, A. I., Mortuza, G. B., Molina, R., Cordeiro, T. N., Castillo, F., Villate, M., Merino, N., Delgado, S., Gil-Cartón, D., Luque, I., Diercks, T., Bernadó, P., Montoya, G., & Blanco, F. J. (2015). Structure of p15^PAF-PCNA complex and implications for clamp sliding during DNA replication and repair. Nature Communications, 6, 1-12. [6439]. https://doi.org/10.1038/ncomms7439

De Biasio, A, de Opakua, AI, Mortuza, GB, Molina, R, Cordeiro, TN, Castillo, F, Villate, M, Merino, N, Delgado, S, Gil-Cartón, D, Luque, I, Diercks, T, Bernadó, P, Montoya, G & Blanco, FJ 2015, 'Structure of p15^PAF-PCNA complex and implications for clamp sliding during DNA replication and repair', Nature Communications, bind 6, 6439, s. 1-12. https://doi.org/10.1038/ncomms7439

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title = "Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair",

abstract = "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.",

author = "{De Biasio}, Alfredo and {de Opakua}, {Alain Ib{\'a}{\~n}ez} and Mortuza, {Gulnahar B} and Rafael Molina and Cordeiro, {Tiago N} and Francisco Castillo and Maider Villate and Nekane Merino and Sandra Delgado and David Gil-Cart{\'o}n and Irene Luque and Tammo Diercks and Pau Bernad{\'o} and Guillermo Montoya and Blanco, {Francisco J}",

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doi = "10.1038/ncomms7439",

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T1 - Structure of p15PAF-PCNA complex and implications for clamp sliding during DNA replication and repair

AU - De Biasio, Alfredo

AU - de Opakua, Alain Ibáñez

AU - Mortuza, Gulnahar B

AU - Molina, Rafael

AU - Cordeiro, Tiago N

AU - Castillo, Francisco

AU - Villate, Maider

AU - Merino, Nekane

AU - Delgado, Sandra

AU - Gil-Cartón, David

AU - Luque, Irene

AU - Diercks, Tammo

AU - Bernadó, Pau

AU - Montoya, Guillermo

AU - Blanco, Francisco J

PY - 2015/3/12

Y1 - 2015/3/12

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms7439

DO - 10.1038/ncomms7439

M3 - Journal article

C2 - 25762514

SN - 2041-1723

VL - 6

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

M1 - 6439

ER -

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

Abstract

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