Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining

Classical non-homologous end-joining (cNHEJ) is the dominant pathway used by human cells to repair DNA double-strand breaks (DSBs) and maintain genome stability. Here the authors show that PARP1-driven chromatin expansion allows the recruitment of ZNF384, which in turn recruits Ku70/Ku80 to facilitate cNHEJ.DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage as they can lead to mutations and chromosomal rearrangements, which underlie cancer development. Classical non-homologous end-joining (cNHEJ) is the dominant pathway for DSB repair in human cells, involving the DNA-binding proteins XRCC6 (Ku70) and XRCC5 (Ku80). Other DNA-binding proteins such as Zinc Finger (ZnF) domain-containing proteins have also been implicated in DNA repair, but their role in cNHEJ remained elusive. Here we show that ZNF384, a member of the C2H2 family of ZnF proteins, binds DNA ends in vitro and is recruited to DSBs in vivo. ZNF384 recruitment requires the poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent expansion of damaged chromatin, followed by binding of its C2H2 motifs to the exposed DNA. Moreover, ZNF384 interacts with Ku70/Ku80 via its N-terminus, thereby promoting Ku70/Ku80 assembly and the accrual of downstream cNHEJ factors, including APLF and XRCC4/LIG4, for efficient repair at DSBs. Altogether, our data suggest that ZNF384 acts as a 'Ku-adaptor' that binds damaged DNA and Ku70/Ku80 to facilitate the build-up of a cNHEJ repairosome, highlighting a role for ZNF384 in DSB repair and genome maintenance.Cancer Signaling networks and Molecular Therapeutic

Construction status and prospects of the Hyper-Kamiokande project

The Hyper-Kamiokande project is a 258-kton Water Cherenkov together with a 1.3-MW high-intensity neutrino beam from the Japan Proton Accelerator Research Complex (J-PARC). The inner detector with 186-kton fiducial volume is viewed by 20-inch photomultiplier tubes (PMTs) and multi-PMT modules, and thereby provides state-of-the-art of Cherenkov ring reconstruction with thresholds in the range of few MeVs. The project is expected to lead to precision neutrino oscillation studies, especially neutrino CP violation, nucleon decay searches, and low energy neutrino astronomy. In 2020, the project was officially approved and construction of the far detector was started at Kamioka. In 2021, the excavation of the access tunnel and initial mass production of the newly developed 20-inch PMTs was also started. In this paper, we present a basic overview of the project and the latest updates on the construction status of the project, which is expected to commence operation in 2027

Prospects for neutrino astrophysics with Hyper-Kamiokande

Hyper-Kamiokande is a multi-purpose next generation neutrino experiment. The detector is a two-layered cylindrical shape ultra-pure water tank, with its height of 64 m and diameter of 71 m. The inner detector will be surrounded by tens of thousands of twenty-inch photosensors and multi-PMT modules to detect water Cherenkov radiation due to the charged particles and provide our fiducial volume of 188 kt. This detection technique is established by Kamiokande and Super-Kamiokande. As the successor of these experiments, Hyper-K will be located deep underground, 600 m below Mt. Tochibora at Kamioka in Japan to reduce cosmic-ray backgrounds. Besides our physics program with accelerator neutrino, atmospheric neutrino and proton decay, neutrino astrophysics is an important research topic for Hyper-K. With its fruitful physics research programs, Hyper-K will play a critical role in the next neutrino physics frontier. It will also provide important information via astrophysical neutrino measurements, i.e., solar neutrino, supernova burst neutrinos and supernova relic neutrino. Here, we will discuss the physics potential of Hyper-K neutrino astrophysics

Diagnostiek in de acute fase van een beroerte: Een eerste normering van de Afasie Bedside Check (ABC)

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