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Chihiro Horigome

Section

Graduate School of Agricultural Science

Job title

Associate Professor

Degree

Ph.D. (Hiroshima University)

researchmap

https://researchmap.jp/10771206

J-GLOBAL ID

201801016986728882

e-Rad No.

10771206

Research History 10

2023/07 - Present

RIKEN
2023/04 - Present

Tohoku University　Graduate School of Agricultural Science Agricultural Chemistry　Associate Professor
2021/07 - 2024/06

Tohoku University
2020/10 - 2023/03

Tohoku University　Graduate School of Agricultural Science Division of Life Science　Assistant Professor
2018/04 - 2020/09

The University of Tokyo　Institute for Quantitative Biosciences　Research Associate
2015/07 - 2018/03

The University of Tokyo　Institute of Molecular and Cellular Biosciences　Research Associate
2010/02 - 2015/06

Friedrich Miescher Institute for Biomedical Research
2009/04 - 2010/01

Hiroshima University　Graduate School of Biosphere Science
2008/04 - 2009/03

Hiroshima University　Graduate School of Biosphere Science
2007/04 - 2008/03

Hiroshima University　Graduate School of Biosphere Science

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Education 3

Hiroshima University　Graduate School of Biosphere Science

2005/04 - 2008/03
Hiroshima University　Graduate School of Biosphere Science

2003/04 - 2005/03
Hiroshima University　Faculty of Applied Biological Science

1999/04 - 2003/03

Committee Memberships 2

酵母遺伝学フォーラム　運営委員

2020/04 - 2026/03
日本農芸化学会　2021年度大会プログラム編成委員

2020 - 2021

Professional Memberships 4

日本遺伝学会

2025/06 - Present
日本農芸化学会

2020/12 - Present
日本分子生物学会

2016/10 - Present
酵母遺伝学フォーラム

2015/08 - Present

Research Areas 1

Life sciences / Molecular biology /

Awards 3

Best Paper Award

2025/09　The Genetics Society of Japan
Genes & Genetic Systems, GGS PRIZE 2023

2023/09　The Genetics Society of Japan　Changed life course upon defective replication of ribosomal RNA genes
酵母遺伝学フォーラム第56回研究報告会会長賞

2023/09　酵母遺伝学フォーラム　相同組換え修復におけるホモロジー・サーチの動態解析

Papers 20

Nuclear pore links Fob1-dependent rDNA damage relocation to lifespan control. International-journal Peer-reviewed

Yamato Okada, Mina Iwaki, Kyosuke Hagiri, Rei Izumi, Masahiko Harata, Chihiro Horigome

FEBS open bio　2026/01/19

DOI： 10.1002/2211-5463.70193 　

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In budding yeast, the replication fork blocking protein Fob1 arrests replication forks at the ribosomal RNA gene (rDNA) locus, leading to DNA double-strand breaks that promote genomic instability and limit replicative lifespan. rDNA damage has been reported to drive exit from the nucleolus, and persistent double-strand breaks can relocate to the nuclear periphery, but how these spatial transitions are organized and how they influence genome stability and aging remain unclear. Here, we analyze the subnuclear localization of a site-specific rDNA break and its functional relationship with nuclear pores. Using quantitative fluorescence microscopy, we show that damaged rDNA accumulates at the nucleolar-nucleoplasmic interface adjacent to the nuclear envelope. This position represents the minimal movement required to leave the nucleolar interior while maintaining contact with the nuclear periphery, in a manner reminiscent of nucleolar caps of higher eukaryotes. Cells defective in nuclear pore association display pronounced rDNA instability that is largely, but not completely, suppressed by deletion of Fob1, with partial restoration of rDNA stability. Disruption of nuclear pore association also shortens replicative lifespan, and this defect is partially rescued by Fob1 deletion, indicating that nuclear pores affect longevity through both Fob1-dependent and Fob1-independent pathways. These findings refine current models of rDNA damage handling in budding yeast and support a role for nuclear pores in spatially organizing Fob1-induced rDNA damage to maintain rDNA stability and replicative lifespan.
核膜を足場としたDNA修復と老化制御の仕組み核膜とリボソームRNA遺伝子から迫る老化の統合理解への挑戦 Invited Peer-reviewed

堀籠智洋

化学と生物　63　(10)　456-462　2025/10
Changed life course upon defective replication of ribosomal RNA genes. International-coauthorship Peer-reviewed

Mei Hattori, Chihiro Horigome, Théo Aspert, Gilles Charvin, Takehiko Kobayashi

Genes & genetic systems　97　(6)　285-295　2023/04/18

DOI： 10.1266/ggs.22-00100 　

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Genome instability is a major cause of aging. In the budding yeast Saccharomyces cerevisiae, instability of the ribosomal RNA gene repeat (rDNA) is known to shorten replicative lifespan. In yeast, rDNA instability in an aging cell is associated with accumulation of extrachromosomal rDNA circles (ERCs) which titrate factors critical for lifespan maintenance. ERC accumulation is not detected in mammalian cells, where aging is linked to DNA damage. To distinguish effects of DNA damage from those of ERC accumulation on senescence, we re-analyzed a yeast strain with a replication initiation defect in the rDNA, which limits ERC multiplication. In aging cells of this strain (rARS-∆3) rDNA became unstable, as in wild-type cells, whereas significantly fewer ERCs accumulated. Single-cell aging analysis revealed that rARS-∆3 cells follow a linear survival curve and can have a wild-type replicative lifespan, although a fraction of the cells stopped dividing earlier than wild type. The doubling time of rARS-∆3 cells appears to increase in the final cell divisions. Our results suggest that senescence in rARS-∆3 is linked to the accumulation of DNA damage as in mammalian cells, rather than to elevated ERC level. Therefore, this strain should be a good model system to study ERC-independent aging.
Analysis of the molecular evolution of histone variant H2A.Z using a linker-mediated complex strategy and yeast genetic complementation International-journal Peer-reviewed

Saho Kitagawa, Masayuki Kusakabe, Daisuke Takahashi, Takumi Narimiya, Yu Nakabayashi, Masayuki Seki, Chihiro Horigome, Masahiko Harata

Bioscience, Biotechnology, and Biochemistry　86　(1)　104-108　2021/12/22
Publisher: Oxford University Press (OUP)
DOI： 10.1093/bbb/zbab190 　

eISSN： 1347-6947

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<title>ABSTRACT</title> The histone variant H2A.Z is deposited into chromatin by specific machinery and is required for genome functions. Using a linker-mediated complex strategy combined with yeast genetic complementation, we demonstrate evolutionary conservation of H2A.Z together with its chromatin incorporation and functions. This approach is applicable to the evolutionary analyses of proteins that form complexes with interactors.
Rejuvenation of ribosomal RNA gene repeats at the nuclear pore Invited Peer-reviewed

Chihiro Horigome, Takehiko Kobayashi

CURRENT GENETICS　66　(1)　7-13　2020/02

DOI： 10.1007/s00294-019-01024-3 　

ISSN： 0172-8083

eISSN： 1432-0983
Ribosomal RNA gene repeats associate with the nuclear pore complex for maintenance after DNA damage. International-journal Peer-reviewed

Chihiro Horigome, Eri Unozawa, Takamasa Ooki, Takehiko Kobayashi

PLoS genetics　15　(4)　e1008103　2019/04

DOI： 10.1371/journal.pgen.1008103 　

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The ribosomal RNA genes (rDNA) comprise a highly repetitive gene cluster. The copy number of genes at this locus can readily change and is therefore one of the most unstable regions of the genome. DNA damage in rDNA occurs after binding of the replication fork blocking protein Fob1 in S phase, which triggers unequal sister chromatid recombination. However, the precise mechanisms by which such DNA double-strand breaks (DSBs) are repaired is not well understood. Here, we demonstrate that the conserved protein kinase Tel1 maintains rDNA stability after replication fork arrest. We show that rDNA associates with nuclear pores, which is dependent on DNA damage checkpoint kinases Mec1/Tel1 and replisome component Tof1. These findings suggest that rDNA-nuclear pore association is due to a replication fork block and subsequent DSB. Indeed, quantitative microscopy revealed that rDNA is relocated to the nuclear periphery upon induction of a DSB. Finally, rDNA stability was reduced in strains where this association with the nuclear envelope was prevented, which suggests its importance for avoiding improper recombination repair that could induce repeat instability.
Asymmetric Processing of DNA Ends at a Double-Strand Break Leads to Unconstrained Dynamics and Ectopic Translocation. International-journal International-coauthorship Peer-reviewed

Isabella Marcomini, Kenji Shimada, Neda Delgoshaie, Io Yamamoto, Andrew Seeber, Anais Cheblal, Chihiro Horigome, Ulrike Naumann, Susan M Gasser

Cell reports　24　(10)　2614-2628　2018/09/04

DOI： 10.1016/j.celrep.2018.07.102 　

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Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress potentially dangerous ectopic recombination. Both sequence and chromatin context are thought to influence pathway choice between non-homologous end-joining (NHEJ) and homology-driven recombination. To test the effect of repetitive sequences on break processing, we have inserted TG-rich repeats on one side of an inducible DSB at the budding yeast MAT locus on chromosome III. Five clustered Rap1 sites within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2 recruitment, impair resection, and favor elongation by telomerase. The two sides of the break lose end-to-end tethering and show enhanced, uncoordinated movement. Only the TG-free side is resected and shifts to the nuclear periphery. In contrast to persistent DSBs without TG repeats that are repaired by imprecise NHEJ, nearly all survivors of repeat-proximal DSBs repair the break by a homology-driven, non-reciprocal translocation from ChrIII-R to ChrVII-L. This suppression of imprecise NHEJ at TG-repeat-flanked DSBs requires the Uls1 translocase activity.
PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL. International-journal International-coauthorship Peer-reviewed

Chihiro Horigome, Denise E Bustard, Isabella Marcomini, Neda Delgoshaie, Monika Tsai-Pflugfelder, Jennifer A Cobb, Susan M Gasser

Genes & development　30　(8)　931-45　2016/04/15

DOI： 10.1101/gad.277665.116 　

ISSN： 0890-9369

eISSN： 1549-5477
SUMO wrestles breaks to the nuclear ring's edge International-coauthorship Invited Peer-reviewed

Chihiro Horigome, Susan M. Gasser

CELL CYCLE　15　(22)　3011-3013　2016

DOI： 10.1080/15384101.2016.1216904 　

ISSN： 1538-4101

eISSN： 1551-4005
Visualizing the spatiotemporal dynamics of DNA damage in budding yeast. International-journal International-coauthorship Invited Peer-reviewed

Chihiro Horigome, Vincent Dion, Andrew Seeber, Lutz R Gehlen, Susan M Gasser

Methods in molecular biology (Clifton, N.J.)　1292　77-96　2015

DOI： 10.1007/978-1-4939-2522-3_6 　

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Fluorescence microscopy has enabled the analysis of both the spatial distribution of DNA damage and its dynamics during the DNA damage response (DDR). Three microscopic techniques can be used to study the spatiotemporal dynamics of DNA damage. In the first part we describe how we determine the position of DNA double-strand breaks (DSBs) relative to the nuclear envelope. The second part describes how to quantify the co-localization of DNA DSBs with nuclear pore clusters, or other nuclear subcompartments. The final protocols describe methods for the quantification of locus mobility over time.
SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. International-journal International-coauthorship Peer-reviewed

Chihiro Horigome, Yukako Oma, Tatsunori Konishi, Roger Schmid, Isabella Marcomini, Michael H Hauer, Vincent Dion, Masahiko Harata, Susan M Gasser

Molecular cell　55　(4)　626-39　2014/08/21

DOI： 10.1016/j.molcel.2014.06.027 　

ISSN： 1097-2765

eISSN： 1097-4164
Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. International-journal International-coauthorship Peer-reviewed

Vincent Dion, Véronique Kalck, Chihiro Horigome, Benjamin D Towbin, Susan M Gasser

Nature cell biology　14　(5)　502-9　2012/04/08

DOI： 10.1038/ncb2465 　

ISSN： 1465-7392
Ribosome biogenesis factors working with a nuclear envelope SUN domain protein New players in the solar system Invited Peer-reviewed

Chihiro Horigome, Keiko Mizuta

NUCLEUS　3　(1)　22-28　2012/01

DOI： 10.4161/nucl.18930 　

ISSN： 1949-1034

eISSN： 1949-1042
Ribosome biogenesis factors bind a nuclear envelope SUN domain protein to cluster yeast telomeres. International-journal International-coauthorship Peer-reviewed

Chihiro Horigome, Takafumi Okada, Kyoko Shimazu, Susan M Gasser, Keiko Mizuta

The EMBO journal　30　(18)　3799-811　2011/08/05

DOI： 10.1038/emboj.2011.267 　

ISSN： 0261-4189
Genetic interaction between ribosome biogenesis and inositol polyphosphate metabolism in Saccharomyces cerevisiae. International-journal Peer-reviewed

Chihiro Horigome, Ryo Ikeda, Takafumi Okada, Kazuhiko Takenami, Keiko Mizuta

Bioscience, biotechnology, and biochemistry　73　(2)　443-6　2009/02

DOI： 10.1271/bbb.80599 　

ISSN： 0916-8451

eISSN： 1347-6947
A ribosome assembly factor Ebp2p, the yeast homolog of EBNA1-binding protein 2, is involved in the secretory response. International-journal Peer-reviewed

Chihiro Horigome, Takafumi Okada, Kana Matsuki, Keiko Mizuta

Bioscience, biotechnology, and biochemistry　72　(4)　1080-6　2008/04

DOI： 10.1271/bbb.70817 　

ISSN： 0916-8451

eISSN： 1347-6947
Yeast Rrp14p is a nucleolar protein involved in both ribosome biogenesis and cell polarity. International-journal Peer-reviewed

Hiroko Yamada, Chihiro Horigome, Takafumi Okada, Chiharu Shirai, Keiko Mizuta

RNA (New York, N.Y.)　13　(11)　1977-87　2007/11

DOI： 10.1261/rna.553807 　

ISSN： 1355-8382
Synergistic defect in 60S ribosomal subunit assembly caused by a mutation of Rrs1p, a ribosomal protein L11-binding protein, and 3'-extension of 5S rRNA in Saccharomyces cerevisiae. International-journal Peer-reviewed

Masanobu Nariai, Tomohisa Tanaka, Takafumi Okada, Chiharu Shirai, Chihiro Horigome, Keiko Mizuta

Nucleic acids research　33　(14)　4553-62　2005

DOI： 10.1093/nar/gki772 　

ISSN： 0305-1048

eISSN： 1362-4962
Ebp2p, the yeast homolog of Epstein-Barr virus nuclear antigen 1-binding protein 2, interacts with factors of both the 60 S and the 40 s ribosomal subunit assembly. International-journal Peer-reviewed

Chiharu Shirai, Tomoko Takai, Masanobu Nariai, Chihiro Horigome, Keiko Mizuta

The Journal of biological chemistry　279　(24)　25353-8　2004/06/11

DOI： 10.1074/jbc.M403338200 　

ISSN： 0021-9258

eISSN： 1083-351X
Rrs1p, a ribosomal protein L11-binding protein, is required for nuclear export of the 60S pre-ribosomal subunit in Saccharomyces cerevisiae. International-journal Peer-reviewed

Keita Miyoshi, Chiharu Shirai, Chihiro Horigome, Kazuhiko Takenami, Junko Kawasaki, Keiko Mizuta

FEBS letters　565　(1-3)　106-10　2004/05/07

DOI： 10.1016/j.febslet.2004.03.087 　

ISSN： 0014-5793

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Misc. 6

Relocation of DNA breaks to nuclear pores is involved in damage-induced sister chromatid cohesion

堀籠智洋, 折原行希, 高橋大輔, 小西辰紀, 尾間由佳子, 島田健士, GASSER Susan M., 原田昌彦

日本農芸化学会大会講演要旨集(Web)　2021　2021

ISSN： 2186-7976
DNA損傷誘導性姉妹染色分体間接着には損傷部位と核膜孔との結合が必要である

岡田大和, 折原行希, 高橋大輔, 小西辰紀, 尾間由佳子, 島田健士, GASSER Susan M., 原田昌彦, 堀籠智洋

日本農芸化学会東北支部大会プログラム・講演要旨集　156th (CD-ROM)　2021
DNA damage-dependent sister chromatid cohesion requires association with nuclear pores

岡田大和, 折原行希, 高橋大輔, 小西辰紀, 尾間由佳子, 原田昌彦, 堀籠智洋

日本分子生物学会年会プログラム・要旨集(Web)　44th　2021
DNA損傷依存的な姉妹染色分体間接着へのSUMO化の関与

折原行希, 尾間由佳子, 小西辰紀, 堀籠智洋, 堀籠智洋, GASSER Susan, 原田昌彦

日本分子生物学会年会プログラム・要旨集(Web)　39th　2016
DNA損傷依存的な姉妹染色分体間接着への核膜タンパク質の関与

折原行希, 尾間由佳子, 小西辰紀, 堀籠智洋, GASSER Susan, 原田昌彦

日本生化学会大会(Web)　88th　2015
DNA二本鎖切断の核膜結合部位決定におけるクロマチン再構成の役割

堀籠智洋, 尾間由佳子, 小西辰紀, SCHMID Roger, SCHMID Roger, MARCOMINI Isabella, MARCOMINI Isabella, HAUER Michael, HAUER Michael, DION Vincent, DION Vincent, 原田昌彦, GASSER Susan M., GASSER Susan M.

日本分子生物学会年会プログラム・要旨集(Web)　37th　2014

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Presentations 34

The nuclear pore complex regulates Rad52-mediated rDNA repair and cellular lifespan in yeast

Yamato Okada, Mina Iwaki, Kyosuke Hagiri, Rei Izumi, Masahiko Harata, Chihiro Horigome

International Symposium on Chromosome Dynamics： from Structure to Cellular Function　2026/06/02
出芽酵母においてリボソームRNA遺伝子に生じたDNA二本鎖切断は、核小体-核質-核膜が交わる領域に移動し、複製寿命を制御する

岡田大和, 岩城美奈, 羽切恭佑, 泉澪, 原田昌彦, 堀籠智洋

第48回日本分子生物学会年会　2025/12/03
Advancing genome editing by controlling donor DNA dynamics in homologous recombination Invited

Aoi Makita, Suzuka Hoshino, Masahiko Harata, Chihiro Horigome

2025/10/08
出芽酵母の相同組換え修復におけるDNA二本鎖切断部位と相同ドナーDNAの動態解析

堀籠智洋, 牧田蒼生, 星野鈴佳, 泉澪, 原田昌彦

日本遺伝学会第97回大会　2025/09/10
DNA二本鎖切断を受けたリボソームRNA遺伝子の動態とその生理的意義

岩城美奈, 岡田大和, 泉澪, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第58回研究報告会　2025/09/04
Visualizing homology search during DNA double-strand break repair in yeast

Chihiro Horigome

GASSER LAB SYMPOSIUM: EXPLORING THE GENOME AND BEYOND　2025/04/05
Visualizing homology search during DNA double-strand break repair in yeast

Aoi Makita, Suzuka Hoshino, Masahiko Harata, Chihiro Horigome

The 12th 3R+3C International Symposium　2024/11/19
相同組換え修復におけるDNA二本鎖切断部位と相同ドナーDNAの動態解析

牧田蒼生, 星野鈴佳, 原田昌彦, 堀籠智洋

日本農芸化学会東北支部第159回大会　2024/09/28
相同組換え修復における相同ドナーDNAの動態解析

牧田蒼生, 星野鈴佳, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第57回研究報告会　2024/09/09
Visualizing homology search during DNA double-strand break repair in yeast Invited

Aoi Makita, Masahiko Harata, Chihiro Horigome

2024/06/20
クライオX線タイコグラフィの開発と生体試料への応用

高山裕貴, 原田康生, 吉田翔庸, 中迫雅由, 岩城美奈, 牧田蒼生, 木浪悠太, 尾間由佳子, 堀籠智洋, 原田昌彦

第37回日本放射光学会年会・放射光科学合同シンポジウム　2024/01/11
出芽酵母の核膜におけるリボソーム RNA 遺伝子の安定維持機構の解明

岡田大和, 蓜島万紘, 原田昌彦, 堀籠智洋

日本農芸化学会東北支部第158回大会　2023/12/02
細胞核内のアクチン繊維がFUSタンパク質の液-液相分離に与える影響の解析

西間木胡桃, 藤井健太郎, 堀籠智洋, 高山裕貴, 原田昌彦

日本農芸化学会東北支部第158回大会　2023/12/02
Visualizing homology search during DNA double strand break repair

Aoi Makita, Masahiko Harata, Chihiro Horigome

2023/10/10
相同組換え修復におけるホモロジー・サーチの動態解析

牧田蒼生, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第56回研究報告会　2023/08/31
出芽酵母のリボソームRNA遺伝子安定性と核膜孔および老化の関係

蓜島万紘, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第56回研究報告会　2023/08/30
出芽酵母の核膜孔におけるリボソームRNA遺伝子安定化メカニズムの解析

岡田大和, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第56回研究報告会　2023/08/30
DNA二本鎖切断部位の核膜結合がゲノム安定化に果たす役割

岡田大和, 堀川和希, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第55回研究報告会　2022/09/07
老化した出芽酵母における DNA 二本鎖切断の核膜結合に関する解析

堀川和希, 原田昌彦, 堀籠智洋

第44回日本分子生物学会年会　2021/12/02
DNA損傷依存的な姉妹染色体分体間接着には核膜孔との結合が必要である

岡田大和, 折原行希, 高橋大輔, 小西辰紀, 尾間由佳子, 島田健士, Susan M. Gasser, 原田昌彦, 堀籠智洋

第44回日本分子生物学会年会　2021/12/02
老化した出芽酵母におけるDNA二本鎖切断の解析

堀川和希, 原田昌彦, 堀籠智洋

日本農芸化学会東北支部第156回大会　2021/10/09
DNA損傷誘導性姉妹染色分体間接着には損傷部位と核膜孔との結合が必要である

岡田大和, 折原行希, 高橋大輔, 小西辰紀, 尾間由佳子, 島田健士, Susan M. Gasser, 原田昌彦, 堀籠智洋

日本農芸化学会東北支部第156回大会　2021/10/09
DNA損傷依存的な姉妹染色分体間接着には核膜孔との結合が必要である

折原行希, 高橋大輔, 小西辰紀, 岡田大和, 尾間由佳子, 島田健士, Susan M. Gasser, 原田昌彦, 堀籠智洋

酵母遺伝学フォーラム第54回研究報告会　2021/08/31
Relocation of DNA breaks to nuclear pores is involved in damage-induced sister chromatid cohesion

2021/03/20
Relocation of DNA breaks to nuclear pores is involved in damage-induced sister chromatid cohesion

2021/01/19
Rejuvenation of ribosomal RNA gene repeats at the nuclear pore

2020/12/01
細胞の老化と若返りを支配する、リボソームRNA遺伝子の不等分配に関する研究

堀籠智洋, 小林武彦

第53回酵母遺伝学フォーラム研究報告会　2020/09/07
DNA二本鎖切断を受けたリボソームRNA遺伝子は核膜孔に結合して安定化される Invited

堀籠智洋, 鵜之沢英理, 大木孝将, 小林武彦

第42回日本分子生物学会年会　2019/12/03
DNA二本鎖切断を受けたリボソームRNA遺伝子は核膜孔に結合して安定化される

堀籠智洋, 鵜之沢英理, 大木孝将, 小林武彦

第52回酵母遺伝学フォーラム研究報告会　2019/09/05
SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice Invited

Chihiro Horigome, Yukako Oma, Tatsunori Konishi, Roger Schmid, Isabella Marcomini, Michael Hauer, Vincent Dion, Masahiko Harata, Susan M. Gasser

2014/11/26
Fob1-dependent binding of ribosomal RNA genes to the nuclear periphery in budding yeast Invited

Chihiro Horigome, Eri Unozawa, Takamasa Ooki, Takehiko Kobayashi

2017/09/21
SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice Invited

Chihiro Horigome, Yukako Oma, Tatsunori Konishi, Roger Schmid, Isabella Marcomini, Michael Hauer, Vincent Dion, Masahiko Harata, Susan M. Gasser

2014/08/19
Ribosome assembly factors, Ebp2 and Rrs1, involved in telomere maintenance with a nuclear envelope SUN protein in budding yeast Invited

Chihiro Horigome, Takafumi Okada, Keiko Mizuta

Switzerland-Japan Joint meeting on the Molecular Mechanisms Regulating Chromosome Dynamics and Genome Stability　2009/05/16
EBP2p IS REQUIRED FOR 60S RIBOSOMAL SUBUNIT BIOGENESIS AND MAINTENANCE OF NUCLEAR SHAPE IN YEAST Invited

Chihiro HORIGOME, Takafumi OKADA, Keiko MIZUTA

2006/08/19

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Research Projects 10

Dynamics of homology search during DNA double-strand break repair

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2025/04 - 2028/03
2026年度交流助成日本招聘

堀籠智洋

Offer Organization: 公益財団法人中谷財団

System: 2026年度交流助成日本招聘

Institution: 東北大学

2026/07 - 2026/12
出芽酵母を用いた革新的な寿命解析法の開発

堀籠智洋

Offer Organization: 内藤記念科学振興財団

System: 内藤記念科学奨励金・研究助成

Institution: 東北大学

2023/12 - 2025/09
細胞核内のアクチン繊維によるゲノム機能制御のメカニズム解明と応用展開

原田昌彦, 堀籠智洋

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(B)

Category: 基盤研究(B)

Institution: 東北大学

2021/04/01 - 2024/03/31
細胞核構造によるゲノム安定化と老化抑制の機構解明

堀籠智洋

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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課題1 核膜結合がrDNA安定化および細胞老化抑制に果たす役割の解明：我々の先行研究により、非rDNA領域であるMAT座でのDNA二本鎖切断が核膜と結合できなくなると、切断誘導性の姉妹染色分体間接着（コヒージョン）の形成に異常が生じることが明らかとなっている。われわれは2021年度に、リボソームRNA遺伝子（rDNA）でDNA二本鎖切断を誘導した時のコヒージョン形成について、顕微鏡を用いた解析により検証した。解析では、rDNA反復配列の1箇所にI-SceI切断部位とtetO配列を導入した株を用い、ガラクトースによりI-SceIエンドヌクレアーゼを発現誘導し、その切断部位をTetI-mRFPにより可視化する株を用いた。通常、DNA複製後のDNA二本鎖切断部位は、コヒージョンにより1つの赤色蛍光輝点として観察されるが、コヒージョンに欠陥がある細胞では2点として観察される。切断誘導後のrDNAが核膜に局在できない変異株において、切断誘導性のコヒージョンに欠陥が見られることを明らかにした。課題2 老化細胞における核膜でのゲノム安定化についての解析：本研究では、MAT遺伝子座にDNA二本鎖切断を誘導できる株を用いて、野生株の老化細胞における核膜とDNA二本鎖切断部位の結合を定量的顕微鏡法により解析する。細胞をビオチン標識した後分裂を繰り返させて細胞を老化させ、ストレプトアビジン磁性ビーズにより老化細胞を選別した。老化細胞においてDNA二本鎖切断の誘導効率が低下することが明らかとなり、その原因が切断をする酵素エンドヌクレアーゼの転写レベルの低下によるものなのか、それとも切断部位のヘテロクロマチン化などに由来するものなのかについて検証を行っている。
Asymmetric inheritance of ribosomal DNA that governs cellular aging and rejuvenation

Horigome Chihiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

2018/04/01 - 2021/03/31

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We have shown that the ribosomal RNA genes (rDNA) in budding yeast are recruited to the nuclear pore upon the induction of DNA double-strand break. In this study, we found that rDNA stability was reduced in strains where this association with the nuclear envelope was prevented. We further showed that rDNA binds to the nuclear pore in a manner dependent on DNA damage checkpoint kinase Tel1 and cohibin which associates rDNA to the nuclear envelope to maintain rDNA stability. We speculate that damaged rDNA is sequestered at the nuclear periphery to inhibit aberrant recombination events.
リボソームRNA遺伝子の核膜結合と不等分配に関する研究

Offer Organization: 公益財団法人住友財団

System: 基礎科学研究助成

Institution: 東京大学、東北大学

2019/12 - 2020/11
Binding of ribosomal RNA genes to the nuclear periphery in budding yeast

Horigome Chihiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: The University of Tokyo

2016/04/01 - 2018/03/31

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The ribosomal RNA genes (rDNA) in budding yeast are organized into a single tandem array of about 150 repeats. Fob1 unidirectionally inhibits replication fork progression at the replication fork barrier and induces DNA double-strand break (DSB) in the rDNA. The DSB leads to unequal sister-chromatid recombination and hence rDNA instability. We performed chromatin immunoprecipitation assay to determine the localization of rDNA within the nucleus. We showed that rDNA binds to the nuclear pore in a manner dependent on Fob1 and DNA damage checkpoint kinase Tel1. The factors which are required for the rDNA-nuclear envelope binding are also important for the rDNA stability. We speculate that Fob1 sequesters rDNA at the nuclear periphery to inhibit aberrant recombination events.
Effect of rDNA instability to chromosome and cellular functions

KOBAYASHI Takehiko, IIDA Tetsushi, AKAMATSU Yufuko, SASAKI Mariko, HORIGOME Chihiro, SAKA Kimiko, HAEIWA Haruna, UNOZAWA Eri, TAKAHASHI Akihiro, WAKATSUKI Tsuyoshi, SUZUKI Yu

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

2011/04/01 - 2016/03/31

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We identified 708 rDNA unstable mutants. The number corresponds to ~10 % of total genes. In one of the rDNA unstable mutants rtt109, that codes a histone acethylase, we found that recombination repair process of damaged rDNA doesn’t work and rolling circle type replication is induced. By analysis of other rDNA unstable mutants, such as tel1, we found that damaged rDNA was relocated to the nuclear pore from nucleolus. The relocation is thought to be important to prevent improper recombination that induces rDNA instability. In terms of the relationship between rDNA stability and lifespan, we got direct evidence that rDNA instability caused by non-coding transcription rDNA reduces replicative lifespan. We also identified some non-coding functional element and the associating proteins in the rDNA in mammalian cells. They inhibit DNA replication and prevent the collision between DNA replication and rDNA transcription.
核構造の安定化に機能を持つリボソーム生合成調節因子に関する研究

堀籠智洋

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特別研究員奨励費

Category: 特別研究員奨励費

Institution: 広島大学

2007 - 2008

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出芽酵母のリボソーム生合成調節因子Ebp2およびRrs1について機能解析を行い、以下の成果を得た。 1.膜輸送経路遮断時におけるシグナル伝達に欠陥を持つrrs1-1の低温感受性を抑圧する変異としてkcs1を見出した。kcs1の変異点を同定し、イノシトール6リン酸キナーゼ領域が欠失する変異であることを明らかにした。kcs1変異およびkcs1破壊が共にrrs1-1における60Sリボソームサブユニットアセンブリの欠陥を抑圧することを示し、イノシトールポリリン酸代謝機構とリボソーム生合成にクロストークが存在することを示唆した。 2.これまでにリボソーム生合成調節因子Ebp2およびRrs1が、真核生物において広く保存されたSUNドメイン蛋白質Mps3との結合を介して核膜に局在することを明らかにしている。Mps3は核内における染色体配置に機能を持つことから、本機構におけるEbp2およびRrs1の関与を調べた。テロメアマーカータンパク質であるRap1と蛍光タンパク質CFPを融合したタンパク質を発現する株を用いた蛍光顕微鏡観察により、Ebp2およびRrs1がテロメアのクラスター形成に関与していることを明らかにした。近年、核膜が転写や修復、さらには老化など、核内における多様な機構に関与していることが報告されている。核膜を足場とした機構とリボソーム生合成との関連についてはこれまでに報告がなく、Ebp2およびRrs1がこれら機構間の連携を解き明かす鍵となることが期待される。

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Media Coverage 1

【東大最前線】細胞若返りの機構解明に期待 rDNAの移動が明らかに

東京大学新聞

2019/07

Type: Newspaper, magazine