EMD-20864

Single-particle
10.5 Å
EMD-20864 Deposition: 27/10/2019
Map released: 14/10/2020
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-20864

Structure of two nucleosomes bridged by human PARP2

EMD-20864

Single-particle
10.5 Å
EMD-20864 Deposition: 27/10/2019
Map released: 14/10/2020
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, synthetic construct
Sample: Two nucleosomes bridged by PARP2
Fitted models: 6usj (Avg. Q-score: 0.092)
Raw data: EMPIAR-10336

Deposition Authors: Gaullier G , Morgan GP, Luger K
Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1.
Gaullier G , Roberts G, Muthurajan UM, Bowerman S, Rudolph J, Mahadevan J , Jha A , Rae PS, Luger K
(2020) PLoS One , 15 , e0240932 - e0240932
PUBMED: 33141820
DOI: doi:10.1371/journal.pone.0240932
ISSN: 1932-6203
Abstract:
Poly(ADP-ribose) Polymerase 2 (PARP2) is one of three DNA-dependent PARPs involved in the detection of DNA damage. Upon binding to DNA double-strand breaks, PARP2 uses nicotinamide adenine dinucleotide to synthesize poly(ADP-ribose) (PAR) onto itself and other proteins, including histones. PAR chains in turn promote the DNA damage response by recruiting downstream repair factors. These early steps of DNA damage signaling are relevant for understanding how genome integrity is maintained and how their failure leads to genome instability or cancer. There is no structural information on DNA double-strand break detection in the context of chromatin. Here we present a cryo-EM structure of two nucleosomes bridged by human PARP2 and confirm that PARP2 bridges DNA ends in the context of nucleosomes bearing short linker DNA. We demonstrate that the conformation of PARP2 bound to damaged chromatin provides a binding platform for the regulatory protein Histone PARylation Factor 1 (HPF1), and that the resulting HPF1•PARP2•nucleosome complex is enzymatically active. Our results contribute to a structural view of the early steps of the DNA damage response in chromatin.