Atsuhiko Fukuto

Hiroshima University

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Regulation of the DNA damage-dependent exchange of histone variant H2A.Z-2

The Japanese Biochemical Society/The Molecular Biology Society of Japan (2017)

Atsuhiko Fukuto Yasunori Horikoshi Satoshi Tashiro

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SUMO E3-ligase PIAS4 regulates DNA damage-dependent exchange of the histone variant H2A.Z-2

The Japanese Biochemical Society/The Molecular Biology Society of Japan (2015)

Atsuhiko Fukuto Yasunori Horikoshi Satoshi Tashiro

SUMO E3-Ligase Regulates DNA Damage-Dependent Exchange of the Histone Variant H2A.Z-2 I. Nishibuchi, S. Tashiro, H. Suzuki, A. Kinomura, J. Sun, M. Harata, T. Fukagawa, T. Ikura, and Y. Nagata; Dep., Cell Bio., RIRBM, Hiroshima Univ., Hiroshima, Japan, Dep., Radiation Oncology, Hiroshima Prefectural Hosp., Hiroshima, Japan, Dep., Biochem., Tohoku Univ., Gr Sch Med., Sendai, Japan, Dep., Mol., Genet., Natl., Inst., Genet., Mishima, Japan, Dep., Mut., RBC., Kyoto Univ., Kyoto, Japan, Dep., Radiation Oncology, Hiroshima Univ., Hiroshima, Japan

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hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair

Genes to Cells (2015)

Satoshi Okimoto Jiying Sun Atsuhiko Fukuto Yasunori Horikoshi Shun Matsuda

Homologous recombinational repair ( HR ) is one of the major repair systems for DNA double‐strand breaks. RAD 51 is a key molecule in HR , and the RAD 51 concentration in the cell nucleus increases after DNA damage induction. However, the mechanism that regulates the intracellular distribution of RAD 51 is still unclear. Here, we show that hCAS / CSE 1L associates with RAD 51 in human cells. We found that hCAS / CSE 1L negatively regulates the nuclear protein level of RAD 51 under normal conditions. hCAS / CSE 1L is also required to repress the DNA damage‐induced focus formation of RAD 51. Moreover, we show that hCAS / CSE 1L plays roles in the regulation of the HR activity and in chromosome stability. These findings suggest that hCAS / CSE 1L is responsible for controlling the HR activity by directly interacting with RAD 51.

10.1111/gtc.12262

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Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations

eLife (2018)

Jiying Sun Lin Shi Aiko Kinomura Atsuhiko Fukuto Yasunori Horikoshi

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities.

10.7554/elife.32222

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Distinctive nuclear zone for RAD51-mediated homologous recombinational DNA repair

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Yasunori Horikoshi Hiroki Shima Jiying Sun Wataru Kobayashi Volker Schmid

Abstract Genome-based functions are inseparable from the dynamic higher-order architecture of the cell nucleus. In this context, the repair of DNA damage is coordinated by precise spatiotemporal controls that target and regulate the repair machinery required to maintain genome integrity. However, the mechanisms that pair damaged DNA with intact template for repair by homologous recombination (HR) without illegitimate recombination remain unclear. This report highlights the intimate relationship between nuclear architecture and HR in mammalian cells. RAD51, the key recombinase of HR, forms spherical foci in S/G 2 phases spontaneously. Using super-resolution microscopy, we show that following induction of DNA double-strand breaks RAD51 foci at damaged sites elongate to bridge between intact and damaged sister chromatids; this assembly occurs within bundle-shaped distinctive nuclear zones, requires interactions of RAD51 with various factors, and precedes ATP-dependent events involved the recombination of intact and damaged DNA. We observed a time-dependent transfer of single-stranded DNA overhangs, generated during HR, into such zones. Our observations suggest that RAD51-mediated homologous pairing during HR takes place within the distinctive nuclear zones to execute appropriate recombination.

10.1101/2021.11.29.470307

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Relaxed Chromatin Formation and Weak Suppression of Homologous Pairing by the Testis-Specific Linker Histone H1T

Biochemistry (2016)

Shinichi Machida Ryota Hayashida Motoki Takaku Atsuhiko Fukuto Jiying Sun

Linker histones bind to nucleosomes and compact polynucleosomes into a higher-order chromatin configuration. Somatic and germ cell-specific linker histone subtypes have been identified and may have distinct functions. In this study, we reconstituted polynucleosomes containing human histones H1.2 and H1T, as representative somatic and germ cell-specific linker histones, respectively, and found that H1T forms less compacted chromatin, as compared to H1.2. An in vitro homologous pairing assay revealed that H1T weakly inhibited RAD51/RAD54-mediated homologous pairing in chromatin, although the somatic H1 subtypes, H1.0, H1.1, H1.2, H1.3, H1.4, and H1.5, substantially suppressed it. An in vivo recombination assay revealed that H1T overproduction minimally affected the recombination frequency, but significant suppression was observed when H1.2 was overproduced in human cells. These results suggested that the testis-specific linker histone, H1T, possesses a specific function to produce the chromatin architecture required for proper chromosome regulation, such as homologous recombination.

10.1021/acs.biochem.5b01126

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Coordinated Regulation of TIP60 and Poly(ADP-Ribose) Polymerase 1 in Damaged-Chromatin Dynamics

Molecular and Cellular Biology (2016)

Masae Ikura Kanji Furuya Atsuhiko Fukuto Ryo Matsuda Jun Adachi

The dynamic exchange of histones alleviates the nucleosome barrier and simultaneously facilitates various aspects of cellular DNA metabolism, such as DNA repair and transcription. In response to DNA damage, the acetylation of Lys5 in the histone variant H2AX, catalyzed by TIP60, plays a key role in promoting histone exchange; however, the detailed molecular mechanism still is unclear. Here, we show that the TIP60 complex includes poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 is required for the rapid exchange of H2AX on chromatin at DNA damage sites. It is known that PARP-1 binds dynamically to damaged chromatin and is crucial for the subsequent recruitment of other repair factors, and its auto-poly(ADP-ribosyl)ation is required for the dynamics. We also show that the acetylation of histone H2AX at Lys5 by TIP60, but not the phosphorylation of H2AX, is required for the ADP-ribosylation activity of PARP-1 and its dynamic binding to damaged chromatin. Our results indicate the reciprocal regulation of K5 acetylation of H2AX and PARP-1, which could modulate the chromatin structure to facilitate DNA metabolism at damage sites. This could explain the rather undefined roles of PARP-1 in various DNA damage responses.

10.1128/mcb.01085-15

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The impact of zinc oxide and vanadium pentoxide nanoparticles on corneal epithelial wound healing in vitro and in vivo

Investigative Ophthalmology & Visual Science (2019)

Atsuhiko Fukuto Soo-Hyun Kim Brooke L. Gates Laura S. Van Winkle Kent E. Pinkerton

Pentoxide

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The impact of reduced graphene oxide on corneal epithelial and fibroblast cells in vitro

Investigative Ophthalmology & Visual Science (2020)

Atsuhiko Fukuto Jennifer Kang Laura S. Van Winkle Kent E. Pinkerton Brian C. Leonard

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Rapid Corneal Calcification Following Endothelial Keratoplasty: A Case Report

Cureus (2024)

Atsuhiko Fukuto Koichiro Shinji Suzu Deie Tai-ichiro Chikama

Corneal calcification typically progresses slowly but can occasionally advance rapidly. This report details severe stromal calcification following repeat Descemet's stripping automated endothelial keratoplasty (DSAEK) in a 75-year-old patient with diabetes, hypertension, and prior ocular surgeries, including cataract surgery, intraocular lens extraction with suturing, and trabeculectomy. Persistent epithelial defects after the surgery led to rapid central stromal calcification within four weeks, significantly reducing visual acuity. Management included switching from betamethasone sodium phosphate to fluorometholone, facilitating complete epithelial recovery within two months. However, persistent stromal opacity necessitated a subsequent penetrating keratoplasty. Infrared absorption spectrophotometry identified calcium phosphate as the primary component of the calcification. This case highlights the importance of vigilant monitoring and proactive management of epithelial defects to prevent rapid calcification following endothelial keratoplasty.

10.7759/cureus.60956

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Citations (1)