| 1. |
- Gaullier, Guillaume, et al.
(författare)
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Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
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Tidskriftsartikel (refereegranskat)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 rel- evant 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 nucleo- somes 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.
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| 2. |
- Gaullier, Guillaume, et al.
(författare)
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PARP1 and Sox2 : An Unlikely Team of Pioneers to Conquer the Nucleosome.
- 2017
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 65:4, s. 581-582
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Tidskriftsartikel (refereegranskat)abstract
- In this issue of Molecular Cell, Liu and Kraus (2017) demonstrate that the pioneer transcription factor Sox2 requires PARP1 to bind to a subset of its recognition motifs, which are located within nucleosomes across the genome.
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| 3. |
- Makowski, Matthew M, et al.
(författare)
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Picking a nucleosome lock : Sequence- and structure-specific recognition of the nucleosome.
- 2020
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Ingår i: Journal of Biosciences. - 0250-5991 .- 0973-7138. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- The nucleosome presents a formidable barrier to DNA-templated transcription by the RNA polymerase II machinery. Overcoming this transcriptional barrier in a locus-specific manner requires sequence-specific recognition of nucleosomal DNA by 'pioneer' transcription factors (TFs). Cell fate decisions, in turn, depend on the coordinated action of pioneer TFs at cell lineage-specific gene regulatory elements. Although it is already appreciated that pioneer factors play a critical role in cell differentiation, our understanding of the structural and biochemical mechanisms by which they act is still rapidly expanding. Recent research has revealed novel insight into modes of nucleosome-TF binding and uncovered kinetic principles by which nucleosomal DNA compaction affects both TF binding and residence time. Here, we review progress and argue that these structural and kinetic studies suggest new models of gene regulation by pioneer TFs.
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| 4. |
- Zhou, Keda, et al.
(författare)
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Nucleosome structure and dynamics are coming of age.
- 2019
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 26:1, s. 3-13
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Tidskriftsartikel (refereegranskat)abstract
- Since the first high-resolution structure of the nucleosome was reported in 1997, the available information on chromatin structure has increased very rapidly. Here, we review insights derived from cutting-edge biophysical and structural approaches applied to the study of nucleosome dynamics and nucleosome-binding factors, with a focus on the experimental advances driving the research. In addition, we highlight emerging challenges in nucleosome structural biology.
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