DNA damage causes checkpoint activation leading to cell cycle arrest and repair, during which the chromatin structure is disrupted. The mechanisms whereby chromatin structure and cell cycle progression are restored after DNA repair are largely unknown. We show that chromatin reassembly following double-strand break (DSB) repair requires the histone chaperone Asf1 and that absence of Asf1 causes cell death, as cells are unable to recover from the DNA damage checkpoint. We find that Asf1 contributes toward chromatin assembly after DSB repair by promoting acetylation of free histone H3 on lysine 56 (K56) via the histone acetyl transferase Rtt109. Mimicking acetylation of K56 bypasses the requirement for Asf1 for chromatin reassembly and checkpoint recovery, whereas mutations that prevent K56 acetylation block chromatin reassembly after repair. These results indicate that restoration of the chromatin following DSB repair is driven by acetylated H3 K56 and that this is a signal for the completion of repair.
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http://dx.doi.org/10.1016/j.cell.2008.06.035 | DOI Listing |
The disassembly and reassembly of nucleosomes by histone chaperones is an essential activity during eukaryotic transcription elongation. This highly conserved process maintains chromatin integrity by transiently removing nucleosomes as barriers and then restoring them in the wake of transcription. While transcription elongation requires multiple histone chaperones, there is little understanding of how most of them function and why so many are required.
View Article and Find Full Text PDFAdv Exp Med Biol
November 2024
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Eukaryotic genome is packaged into chromatin. Thus, transcription takes place in the context of chromatin that is an array of nucleosomes. Nucleosome poses a barrier for the gene regulatory factors to access DNA for transcription to occur.
View Article and Find Full Text PDFJ Virol
August 2024
Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Facilitates chromatin transcription (FACT) interacts with nucleosomes to promote gene transcription by regulating the dissociation and reassembly of nucleosomes downstream and upstream of RNA polymerase II (Pol II). A previous study reported that herpes simplex virus 1 (HSV-1) regulatory protein ICP22 interacted with FACT and was required for its recruitment to the viral DNA genome in HSV-1-infected cells. However, the biological importance of interactions between ICP22 and FACT in relation to HSV-1 infection is unclear.
View Article and Find Full Text PDFNucleic Acids Res
December 2023
Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona 08003, Spain.
Chromatin remodeling is essential to allow full development of alternative gene expression programs in response to environmental changes. In fission yeast, oxidative stress triggers massive transcriptional changes including the activation of hundreds of genes, with the participation of histone modifying complexes and chromatin remodelers. DNA transcription is associated to alterations in DNA topology, and DNA topoisomerases facilitate elongation along gene bodies.
View Article and Find Full Text PDFMethods Mol Biol
October 2023
Department of Physics, Northeastern University, Boston, MA, USA.
The dynamics of histone-DNA interactions govern chromosome organization and regulates the processes of transcription, replication, and repair. Accurate measurements of the energies and the kinetics of DNA binding to component histones of the nucleosome under a variety of conditions are essential to understand these processes at the molecular level. To accomplish this, we employ three specific single-molecule techniques: force disruption (FD) with optical tweezers, confocal imaging (CI) in a combined fluorescence plus optical trap, and survival probability (SP) measurements of disrupted and reformed nucleosomes.
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