TOHOKU UNIVERSITY Researchers

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Ayako Ui

Section

Institute of Development, Aging and Cancer

Job title

Associate Professor

Degree

博士（薬学）（東北大学）
修士（薬学）（東北大学）

researchmap

https://researchmap.jp/uia

J-GLOBAL ID

201801009357880268

e-Rad No.

00469967

Research History 7

2020/04 - 2024/03

Nagoya University
2016/10/01 - 2019/09/30

Tokyo University of Technology　School of Bioscience and Biotechnology, Department of Bioscience and Biotechnology
2016/04 - 2017/03

Lecturer
2015/01 - 2016/09

Lecturer
2010/04 - 2014/12

Assistant Professor
2006/04 - 2010/03

Researcher
2003/04 - 2006/03

Special researcher of the Japan Society for the Promotion of Science

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Professional Memberships 6

日本放射線影響学会
日本遺伝学会
癌学会
生化学会
薬学会
分子生物学会

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Research Interests 3

クロマチンリモデリング
転写
DNA修復

Research Areas 4

Life sciences / Molecular biology /
Environmental science/Agricultural science / Environmental effects of chemicals /
Environmental science/Agricultural science / Environmental effects of radiation /
Life sciences / Pharmaceuticals - health and biochemistry /

Papers 38

A novel method for endometrial cancer patient stratification considering ARID1A protein expression and activity with effective use of multi-omics data Peer-reviewed

Junsoo Song, Ayako Ui, Kenji Mizuguchi, Reiko Watanabe

Computational and Structural Biotechnology Journal　27　2614-2625　2025/06
Publisher: Elsevier BV
DOI： 10.1016/j.csbj.2025.06.015 　

ISSN： 2001-0370
Armadillo domain of ARID1A directly interacts with DNA-PKcs to couple chromatin remodeling with nonhomologous end joining (NHEJ) pathway. International-journal Peer-reviewed

Shin-Ichiro Kanno, Takayasu Kobayashi, Reiko Watanabe, Akihiro Kurimasa, Kozo Tanaka, Akira Yasui, Ayako Ui

Nucleic acids research　53　(5)　2025/02/27

DOI： 10.1093/nar/gkaf150 　

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The SWI/SNF chromatin-remodeling complex that comprises multiple subunits orchestrates diverse cellular processes, including gene expression, DNA repair, and DNA replication, by sliding and releasing nucleosomes. AT-interacting domain-rich protein 1A (ARID1A) and ARID1B (ARID1A/B), a pivotal subunit, have significant relevance in cancer management because they are frequently mutated in a broad range of cancer types. To delineate the protein network involving ARID1A/B, we investigated the interactions of this with other proteins under physiological conditions. The ARID domain of ARID1A/B interacts with proteins involved in transcription and DNA/RNA metabolism. Several proteins are responsible for genome integrity maintenance, including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), bound to the armadillo (ARM) domain of ARID1A/B. Introducing a knock-in mutation at the binding amino acid of DNA-PKcs in HCT116 cells reduced the autophosphorylation of DNA-PKcs and the recruitment of LIG4 in response to ionizing radiation. Our findings suggest that within the SWI/SNF complex, ARID1A couples DNA double-strand break repair processes with chromatin remodeling via the ARM domains to directly engage with DNA-PKcs to maintain genome stability.
CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency. International-journal Peer-reviewed

Yujiro Yoshizaki, Yunosuke Ouchi, Dicky Kurniawan, Eisuke Yumoto, Yuki Yoneyama, Faiza Ramadhani Rizqullah, Hiyori Sato, Mirjam Hanako Sarholz, Toyoaki Natsume, Masato T Kanemaki, Masanori Ikeda, Ayako Ui, Kenji Iemura, Kozo Tanaka

Scientific reports　14　(1)　31904-31904　2024/12/30

DOI： 10.1038/s41598-024-83435-y 　

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CHAMP1 (chromosome alignment-maintaining phosphoprotein 1) plays a role in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The CHAMP1 gene is one of the genes mutated in individuals with intellectual disability. The majority of the mutations are premature termination codon (PTC) mutations, while missense mutations have also been reported. How these mutations affect the functions of CHAMP1 has not been clarified yet. Here we investigated the effects of the CHAMP1 mutations on HR. In Epstein-Barr virus-induced lymphoblastoid cells and fibroblasts derived from individuals with CHAMP1 PTC mutations, truncated CHAMP1 proteins of the expected sizes were detected. When DSBs were induced in fibroblasts with PTC mutations, a defect in HR was detected. U2OS cells expressing the CHAMP1 mutants did not show an HR defect in the presence of endogenous wild-type (WT) CHAMP1, whereas they were unable to restore HR activity when CHAMP1 WT was depleted, suggesting that the PTC mutations are loss-of-function mutations. On the other hand, the CHAMP1 mutants with missense mutations restored HR activity when CHAMP1 WT was depleted. In DLD-1 cells, heterozygous depletion of CHAMP1 resulted in an HR defect, indicating haploinsufficiency. These results suggest that CHAMP1 PTC mutations cause an HR defect through a haploinsufficient mechanism, while CHAMP1 missense mutations do not affect the HR function of CHAMP1.
Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis. International-journal Peer-reviewed

Junya Tabata, Takashi Nakaoku, Mitsugu Araki, Ryunosuke Yoshino, Shinji Kohsaka, Ayaka Otsuka, Masachika Ikegami, Ayako Ui, Shin-Ichiro Kanno, Keiko Miyoshi, Shigeyuki Matsumoto, Yukari Sagae, Akira Yasui, Masakazu Sekijima, Hiroyuki Mano, Yasushi Okuno, Aikou Okamoto, Takashi Kohno

Cancer research　82　(20)　3751-3762　2022/10/17

DOI： 10.1158/0008-5472.CAN-22-0834 　

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Distinguishing oncogenic mutations from variants of unknown significance (VUS) is critical for precision cancer medicine. Here, computational modeling of 71,756 RET variants for positive selection together with functional assays of 110 representative variants identified a three-dimensional cluster of VUSs carried by multiple human cancers that cause amino acid substitutions in the calmodulin-like motif (CaLM) of RET. Molecular dynamics simulations indicated that CaLM mutations decrease interactions between Ca2+ and its surrounding residues and induce conformational distortion of the RET cysteine-rich domain containing the CaLM. RET-CaLM mutations caused ligand-independent constitutive activation of RET kinase by homodimerization mediated by illegitimate disulfide bond formation. RET-CaLM mutants possessed oncogenic and tumorigenic activities that could be suppressed by tyrosine kinase inhibitors targeting RET. This study identifies calcium-binding ablating mutations as a novel type of oncogenic mutation of RET and indicates that in silico-driven annotation of VUSs of druggable oncogenes is a promising strategy to identify targetable driver mutations. SIGNIFICANCE: Comprehensive proteogenomic and in silico analyses of a vast number of VUSs identify a novel set of oncogenic and druggable mutations in the well-characterized RET oncogene.
BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal Aurora A. International-journal Peer-reviewed

Huicheng Qi, Megumi Kikuchi, Yuki Yoshino, Zhenzhou Fang, Kazune Ohashi, Takato Gotoh, Ryo Ideta, Ayako Ui, Shino Endo, Kei Otsuka, Norihisa Shindo, Kohsuke Gonda, Chikashi Ishioka, Yoshio Miki, Tokuro Iwabuchi, Natsuko Chiba

Cancer science　113　(12)　4230-4243　2022/09/09

DOI： 10.1111/cas.15573 　

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Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage-induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S-G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo-like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient-derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP-induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
CHAMP1-POGZ counteracts the inhibitory effect of 53BP1 on homologous recombination and affects PARP inhibitor resistance International-journal Peer-reviewed

Hiroki Fujita, Masanori Ikeda, Ayako Ui, Yunosuke Ouchi, Yoshiko Mikami, Shin-ichiro Kanno, Akira Yasui, Kozo Tanaka

Oncogene　41　(19)　2706-2718　2022/04/07
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41388-022-02299-6 　

ISSN： 0950-9232

eISSN： 1476-5594

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DNA double-strand break (DSB) repair-pathway choice regulated by 53BP1 and BRCA1 contributes to genome stability. 53BP1 cooperates with the REV7-Shieldin complex and inhibits DNA end resection to block homologous recombination (HR) and affects the sensitivity to inhibitors for poly (ADP-ribose) polymerases (PARPs) in BRCA1-deficient cells. Here, we show that a REV7 binding protein, CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), has an opposite function of REV7 in DSB repair and promotes HR through DNA end resection together with POGZ (POGO transposable element with ZNF domain). CHAMP1 was recruited to laser-micro-irradiation-induced DSB sites and promotes HR, but not NHEJ. CHAMP1 depletion suppressed the recruitment of BRCA1, but not the recruitment of 53BP1, suggesting that CHAMP1 regulates DSB repair pathway in favor of HR. Depletion of either CHAMP1 or POGZ impaired the recruitment of phosphorylated RPA2 and CtIP (CtBP-interacting protein) at DSB sites, implying that CHAMP1, in complex with POGZ, promotes DNA end resection for HR. Furthermore, loss of CHAMP1 and POGZ restored the sensitivity to a PARP inhibitor in cells depleted of 53BP1 together with BRCA1. These data suggest that CHAMP1and POGZ counteract the inhibitory effect of 53BP1 on HR by promoting DNA end resection and affect the resistance to PARP inhibitors.
Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair. International-journal

Takeshi Yasuda, Kazuya Takizawa, Ayako Ui, Michio Hama, Wataru Kagawa, Kaoru Sugasawa, Katsushi Tajima

Genes to cells : devoted to molecular & cellular mechanisms　26　(5)　328-335　2021/02/23

DOI： 10.1111/gtc.12842 　

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SIRT2 and SIRT3 protein deacetylases maintain genome integrity and stability. However, their mechanisms for maintaining the genome remain unclear. To examine the roles of SIRT2 and SIRT3 in DSB repair, I-SceI-based GFP reporter assays for HR, single-strand annealing (SSA) and nonhomologous end joining (NHEJ) repair were performed under SIRT2- or SIRT3-depleted conditions. SIRT2 or SIRT3 depletion inhibited HR repair equally to RAD52 depletion, but did not affect SSA and NHEJ repairs. SIRT2 or SIRT3 depletion disturbed the recruitment of RAD51 to DSB sites, an essential step for RAD51-dependent HR repair, but not directly through RAD52 deacetylation. SIRT2 or SIRT3 depletion decreased the colocalization of γH2AX foci with RPA1, and thus, they might be involved in initiating DSB end resection for the recruitment of RAD51 to DSB sites at an early step in HR repair. These results show the novel underlying mechanism of the SIRT2 and SIRT3 functions in HR for genome stability.
Relationship among DNA double‐strand break (DSB), DSB repair, and transcription prevents genome instability and cancer International-journal Invited Peer-reviewed

Ayako Ui, Natsuko Chiba, Akira Yasui

Cancer Science　111　(5)　1443-1451　2020/05
Publisher: Wiley
DOI： 10.1111/cas.14404 　

ISSN： 1347-9032

eISSN： 1349-7006

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DNA double-strand break (DSB) is a serious type of DNA damage and is known to trigger multiple responses within cells. In these responses, novel relationships among DSB, DSB repair, and transcription machineries are created. First, transcription is repressed if DSB occurs near or at the transcription site, termed DSB-induced transcriptional repression, which contributes to DSB repair with the aid of DNA damage-signaling pathways, ATM- or DNA-PKcs-signaling pathways. DSB-induced transcriptional repression is also regulated by transcriptional factors TLP1, NELF, and ENL, as well as chromatin remodeling and organizing factors ZMYND8, CDYL1, PBAF, and cohesin. Second, transcription and RNA promote DSB repair for genome integrity. Transcription factors such as LEDGF, SETD2, and transcriptionally active histone modification, H3K36, facilitate homologous recombination to overcome DSB. At transcriptional active sites, DNA:RNA hybrids, termed R-loops, which are formed by DSB, are processed by RAD52 and XPG leading to an activation of the homologous recombination pathway. Even in a transcriptionally inactive non-genic sites, noncoding RNAs that are produced by RNA polymerase II, DICER, and DROSHA, help to recruit DSB repair proteins at the DSB sites. Third, transcriptional activation itself, however, can induce DSB. Transcriptional activation often generates specific DNA structures such as R-loops and topoisomerase-induced DSBs, which cause genotoxic stress and may lead to genome instability and consequently to cancer. Thus, transcription and DSB repair machineries interact and cooperate to prevent genome instability and cancer.
Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. International-journal Peer-reviewed

Takeshi Yasuda, Wataru Kagawa, Tomoo Ogi, Takamitsu A Kato, Takehiro Suzuki, Naoshi Dohmae, Kazuya Takizawa, Yuka Nakazawa, Matthew D Genet, Mika Saotome, Michio Hama, Teruaki Konishi, Nakako Izumi Nakajima, Masaharu Hazawa, Masanori Tomita, Manabu Koike, Katsuko Noshiro, Kenichi Tomiyama, Chizuka Obara, Takaya Gotoh, Ayako Ui, Akira Fujimori, Fumiaki Nakayama, Fumio Hanaoka, Kaoru Sugasawa, Ryuichi Okayasu, Penny A Jeggo, Katsushi Tajima

PLoS genetics　14　(3)　e1007277　2018/03
Publisher: PLOS
DOI： 10.1371/journal.pgen.1007277 　

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The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism.
Erratum: Author Correction: Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair (Nature communications (2017) 8 (16102)) International-journal Peer-reviewed

Niida H, Matsunuma R, Horiguchi R, Uchida C, Nakazawa Y, Motegi A, Nishimoto K, Sakai S, Ohhata T, Kitagawa K, Moriwaki S, Nishitani H, Ui A, Ogi T, Kitagawa M

Nature communications　9　16214-16214　2018

DOI： 10.1038/ncomms16214 　
Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair International-journal Peer-reviewed

Hiroyuki Niida, Ryoichi Matsunuma, Ryo Horiguchi, Chiharu Uchida, Yuka Nakazawa, Akira Motegi, Koji Nishimoto, Satoshi Sakai, Tatsuya Ohhata, Kyoko Kitagawa, Shinichi Moriwaki, Hideo Nishitani, Ayako Ui, Tomoo Ogi, Masatoshi Kitagawa

NATURE COMMUNICATIONS　8　16214-16214　2017/07

DOI： 10.1038/ncomms16102 　

ISSN： 2041-1723
Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing International-journal Peer-reviewed

Reiko Watanabe, Shin-Ichiro Kanno, Amaneh Mohammadi Roushandeh, Ayako Ui, Akira Yasui

Philosophical Transactions of the Royal Society B: Biological Sciences　372　(1731)　2017
Publisher: Royal Society Publishing
DOI： 10.1098/rstb.2016.0473 　

ISSN： 1471-2970 0962-8436
Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity International-journal Invited Peer-reviewed

Ayako Ui, Akira Yasui

NUCLEUS　7　(2)　138-145　2016

DOI： 10.1080/19491034.2016.1177681 　

ISSN： 1949-1034

eISSN： 1949-1042
Transcriptional Elongation Factor ENL Phosphorylated by ATM Recruits Polycomb and Switches Off Transcription for DSB Repair International-journal Peer-reviewed

Ayako Ui, Yuko Nagaura, Akira Yasui

MOLECULAR CELL　58　(3)　468-482　2015/05

DOI： 10.1016/j.molcel.2015.03.023 　

ISSN： 1097-2765

eISSN： 1097-4164
SWI/SNF Factors Required for Cellular Resistance to DNA Damage Include ARID1A and ARID1B and Show Interdependent Protein Stability International-journal Peer-reviewed

Reiko Watanabe, Ayako Ui, Shin-ichiro Kanno, Hideaki Ogiwara, Takahiro Nagase, Takashi Kohno, Akira Yasui

CANCER RESEARCH　74　(9)　2465-2475　2014/05

DOI： 10.1158/0008-5472.CAN-13-3608 　

ISSN： 0008-5472

eISSN： 1538-7445
Possible involvement of LKB1-AMPK signaling in non-homologous end joining Peer-reviewed

A. Ui, H. Ogiwara, S. Nakajima, S. Kanno, R. Watanabe, M. Harata, H. Okayama, C. C. Harris, J. Yokota, A. Yasui, T. Kohno

ONCOGENE　33　(13)　1640-1648　2014/03

DOI： 10.1038/onc.2013.125 　

ISSN： 0950-9232

eISSN： 1476-5594
Fine-Tuning of DNA Damage-Dependent Ubiquitination by OTUB2 Supports the DNA Repair Pathway Choice International-journal Peer-reviewed

Kiyoko Kato, Kazuhiro Nakajima, Ayako Ui, Yuri Muto-Terao, Hideaki Ogiwara, Shinichiro Nakada

MOLECULAR CELL　53　(4)　617-630　2014/02

DOI： 10.1016/j.molcel.2014.01.030 　

ISSN： 1097-2765

eISSN： 1097-4164
Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor International-journal Peer-reviewed

Hideaki Ogiwara, Ayako Ui, Bunsyo Shiotani, Lee Zou, Akira Yasui, Takashi Kohno

CARCINOGENESIS　34　(11)　2486-2497　2013/11

DOI： 10.1093/carcin/bgt240 　

ISSN： 0143-3334

eISSN： 1460-2180
クロマチンリモデリングとDNA二重鎖切断修復・がん Invited Peer-reviewed

宇井彩子

放射線生物研究　2013
Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors Peer-reviewed

H. Ogiwara, A. Ui, A. Otsuka, H. Satoh, I. Yokomi, S. Nakajima, A. Yasui, J. Yokota, T. Kohno

ONCOGENE　30　(18)　2135-2146　2011/05

DOI： 10.1038/onc.2010.592 　

ISSN： 0950-9232
The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells International-journal Peer-reviewed

Li Lan, Ayako Ui, Satoshi Nakajima, Kotomi Hatakeyama, Mikiko Hoshi, Reiko Watanabe, Susan M. Janicki, Hideaki Ogiwara, Takashi Kohno, Shin-ichiro Kanno, Akira Yasui

MOLECULAR CELL　40　(6)　976-987　2010/12

DOI： 10.1016/j.molcel.2010.12.003 　

ISSN： 1097-2765
Rad52 sumoylation and its involvement in the efficient induction of homologous recombination International-journal Peer-reviewed

Takashi Ohuchi, Masayuki Seki, Dana Branzei, Daisuke Maeda, Ayako Ui, Hideaki Ogiwara, Shusuke Tada, Takemi Enomoto

DNA REPAIR　7　(6)　879-889　2008/06

DOI： 10.1016/j.dnarep.2008.02.005 　

ISSN： 1568-7864
Ctf18 is required for homologous recombination-mediated double-strand break repair International-journal Peer-reviewed

Hideaki Ogiwara, Takashi Ohuchi, Ayako Ui, Shusuke Tada, Takemi Enomoto, Masayuki Seki

NUCLEIC ACIDS RESEARCH　35　(15)　4989-5000　2007/08

DOI： 10.1093/nar/gkm523 　

ISSN： 0305-1048

eISSN： 1362-4962
Actin-related protein Arp4 functions in kinetochore assembly International-journal Peer-reviewed

Hideaki Ogiwara, Ayako Ui, Satoshi Kawashima, Kazuto Kugou, Fumitoshi Onoda, Hitoshi Iwahashi, Masahiko Harata, Kunihiro Ohta, Takemi Enomoto, Masayuki Seki

NUCLEIC ACIDS RESEARCH　35　(9)　3109-3117　2007/05

DOI： 10.1093/nar/gkm161 　

ISSN： 0305-1048

eISSN： 1362-4962
Ames test-negative carcinogen, ortho-phenyl phenol, binds tubulin and causes aneuploidy in budding yeast International-journal Peer-reviewed

Tatsuo Nunoshiba, Eri Watanabe, Teruhisa Takahashi, Yasukazu Daigaku, Satoko Ishikawa, Masataka Mochizuki, Ayako Ui, Takemi Enomoto, Kazuo Yamamoto

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS　617　(1-2)　90-97　2007/04

DOI： 10.1016/j.mrfmmm.2007.01.002 　

ISSN： 0027-5107
Rad50 is involved in MMS-induced recombination between homologous chromosomes in mitotic cells Peer-reviewed

Yuji Tomizawa, Ayako Ui, Fumitoshi Onoda, Hideaki Ogiwara, Shusuke Tada, Takemi Enomoto, Masayuki Seki

GENES & GENETIC SYSTEMS　82　(2)　157-160　2007/04

ISSN： 1341-7568

eISSN： 1880-5779
Chl1 and Ctf4 are required for damage-induced recombinations International-journal Peer-reviewed

Hideaki Ogiwara, Ayako Ui, Mong Sing Lai, Takemi Enomoto, Masayuki Seki

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　354　(1)　222-226　2007/03

DOI： 10.1016/j.bbrc.2006.12.185 　

ISSN： 0006-291X
Activation of a novel pathway involving Mms1 and Rad59 in sgs1 cells International-journal Peer-reviewed

Ayako Ui, Masayuki Seki, Hideaki Ogiwara, Mong Sing Lai, Kazuo Yamamoto, Shusuke Tada, Takemi Enomoto

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　356　(4)　1031-1037　2007

DOI： 10.1016/j.bbrc.2007.03.088 　

ISSN： 0006-291X
Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion. International-journal Peer-reviewed

Mong Sing Lai, Masayuki Seki, Ayako Ui, Takemi Enomoto

EMBO reports　8　(7)　685-90　2007

ISSN： 1469-221X

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The Saccharomyces cerevisiae RecQ-mediated genome instability (Rmi1) protein was recently identified as the third member of the slow growth suppressor 1-DNA topoisomerase III (Sgs1-Top3) complex, which is required for maintaining genomic stability. Here, we show that cells lacking RMI1 have a mitotic delay, which is partly dependent on the spindle checkpoint, and are sensitive to the microtubule depolymerizing agent benomyl. We show that rmi1 and top3 single mutants are defective in sister chromatid cohesion, and that deletion of SGS1 suppresses benomyl sensitivity and the cohesion defect in these mutant cells. Loss of RAD51 also suppresses the cohesion defect of rmi1 mutant cells. These results indicate the existence of a new pathway involving Rad51 and Sgs1-Top3-Rmi1, which leads to the establishment of sister chromatid cohesion.
Role of Elg1 protein in double strand break repair. International-journal Peer-reviewed

Hideaki Ogiwara, Ayako Ui, Takemi Enomoto, Masayuki Seki

Nucleic acids research　35　(2)　353-62　2007

eISSN： 1362-4962

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The inaccurate repair of DNA double-strand breaks (DSBs) can result in genomic instability, and additionally cell death or the development of cancer. Elg1, which forms an alternative RFC-like complex with RFC2-5, is required for the maintenance of genome stability in Saccharomyces cerevisiae, and its function has been linked to DNA replication or damage checkpoint response. Here, we show that Elg1 is involved in homologous recombination (HR)-mediated DSB repair. Mutants of elg1 were partially defective in HR induced by methylmethanesufonate (MMS) and phleomycin. Deletion of ELG1 resulted in less efficient repair of phleomycin-induced DSBs in G2/M phase-arrested cells. During HR between MAT and HML loci, Elg1 associated with both the MAT locus near the HO endonuclease-induced DSB site, and the HML homologous donor locus. The association of Elg1 with the MAT locus was not dependent on Rad52. However, Elg1 association with the HML locus depended on Rad52. Importantly, we found that two of the later steps in HR-mediated repair of an HO endonuclease-induced DSB, primer extension after strand invasion and ligation, were less efficient in elg1 mutants. Our results suggest that Elg1 is involved in DSB repair by HR.
Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle International-journal Peer-reviewed

Yasukazu Daigaku, Satsuki Mashiko, Keiichiro Mishiba, Saburo Yamamura, Ayako Ui, Takemi Enomoto, Kazuo Yamamoto

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS　600　(1-2)　177-183　2006/08

DOI： 10.1016/j.mrfmmm.2006.04.001 　

ISSN： 0027-5107
Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair Peer-reviewed

Ogiwara H, Ui A, Onoda F, Tada S, Enomoto T, Seki M

Nucleic Acids Research　2006
The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination International-journal Peer-reviewed

Ayako Ui, Masayuki Seki, Hideaki Ogiwara, Ryoko Onodera, Shin-Ichi Fukushige, Fumitoshi Onoda, Takemi Enomoto

DNA Repair　4　(2)　191-201　2005/02/03

DOI： 10.1016/j.dnarep.2004.09.002 　

ISSN： 1568-7864
RecQファミリーヘリカーゼのDNA複製、DNA修復における機能

宇井彩子, 榎本武美

放射線生物研究　40　(1)　14-25　2005
Publisher: 放射線生物研究会
ISSN： 0441-747X
SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae International-journal Peer-reviewed

F Onoda, M Takeda, M Seki, D Maeda, JI Tajima, A Ui, H Yagi, T Enomoto

DNA REPAIR　3　(4)　429-439　2004/04

DOI： 10.1016/j.dnarep.2003.12.007 　

ISSN： 1568-7864
Functional and physical interaction between Sgs1 and Top3 and Sgs1-independent function of Top3 in DNA recombination repair Peer-reviewed

R Onodera, M Seki, A Ui, Y Satoh, A Miyajima, F Onoda, T Enomoto

GENES & GENETIC SYSTEMS　77　(1)　11-21　2002/02

ISSN： 1341-7568

eISSN： 1880-5779
The N-terminal region of Sgs1, which interacts with Top3, is required for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 disruptants Peer-reviewed

A Ui, Y Satoh, F Onoda, A Miyajima, M Seki, T Enomoto

MOLECULAR GENETICS AND GENOMICS　265　(5)　837-850　2001/07

DOI： 10.1007/s004380100479 　

ISSN： 1617-4615
Different domains of Sgs1 are required for mitotic and meiotic functions Peer-reviewed

A Miyajima, M Seki, F Onoda, A Ui, Y Satoh, Y Ohno, T Enomoto

GENES & GENETIC SYSTEMS　75　(6)　319-326　2000/12

ISSN： 1341-7568

eISSN： 1880-5779

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Misc. 10

Chromatin remodeler, ISWI, moves nucleosomes to promote Homologous Recombination, and mobilizes DNA polymerase at DSBs.

宇井彩子

第41回染色体ワークショップ・第22回核ダイナミクス研究会要旨集　2024/01
Transcription–replication conflictsにおけるクロマチン構造変化とDNA修復経路

宇井彩子

日本分子生物学会年会プログラム要旨集　2023/12
A BET-family protein BRD3 is involved in Homologous recombination and affects PARP inhibitor resistance.

Qian Jianghao, Reiko Watanabe, Tomoko Watanabe, Kozo Tanaka, Takashi Kohno, Akira Yasui, Ayako Ui

2023/09
Chromatin remodeler, ISWI, alters chromatin structure to promote Homologous Recombination, mobilizing DNA polymerase at DSBs

第27回 DNA複製・組換え・修復ワークショップ要旨集　2023/06
クロマチンリモデリング複合体ISWIのHRにおける機能

宇井彩子

第10回ＤＮＡ損傷応答ワークショップ要旨集　2023/04
Identification of novel druggable mutations of RET kinase -Novel activation mode of RET kinase protein-

Junya Tabata, Takashi Nakaoku, Kosuke Maruyama, Shigenari Nukaga, Ayako Ui, Takashi Kohno

CANCER SCIENCE　113　684-684　2022/02

ISSN： 1347-9032

eISSN： 1349-7006
RETキナーゼにおける新たな治療標的変異の同定 RETキナーゼ蛋白質の新たな活性化機構

田畑潤哉, 中奥敬史, 丸山宏輔, 額賀重成, 宇井彩子, 河野隆志

日本癌学会総会記事　80回　[J4-5]　2021/09
Publisher: (一社)日本癌学会
ISSN： 0546-0476
BRCA1はDNA単鎖切断修復に関与する

柏木梨佐, 古川裕美子, 魏雷震, 宇井彩子, 松澤綾子, 柵木絵美子, 柴田峻, 石岡千加史, 安井明, 千葉奈津子

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　83回・33回　2P-0461　2010/12
Publisher: (公社)日本生化学会
Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair International-journal

Hideaki Ogiwara, Ayako Ui, Fumitoshi Onoda, Shusuke Tada, Takemi Enomoto, Masayuki Seki

NUCLEIC ACIDS RESEARCH　34　(11)　3389-3398　2006

DOI： 10.1093/nar/gkl411 　

ISSN： 0305-1048

eISSN： 1362-4962
Analysis of functional domain of budding yeast Sgs1p

SATOH Yurie, ONODERA Ryoko, ONODA Fumitoshi, UI Ayako, MIYAJIMA Masayuki, SEKI Masayuki, ENOMOTO Takemi

21　387-387　1998/12/01

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Presentations 34

Armadillo domain of ARID1A directly interacts with DNA-PKcs to couple chromatin remodeling with nonhomologous end joining (NHEJ) pathway.

2025/01
Novel protein networks involving ARID1A and ARID1B in SWI/SNF complex, and its functions in genome stability. Invited

Shin-ichiro Kanno, Takayasu Kobayashi, Reiko Watanabe, Akihiro Kurimasa, Kozo Tanaka, Akira Yasui, Ayako Ui

2024/11
Novel protein networks involving ARID1A and ARID1B in SWI/SNF complex, and its functions in genome stability

2024/09
Chromatin remodeler, ISWI, moves nucleosomes to promote Homologous Recombination, and mobilizes DNA polymerase at DSBs.

宇井彩子, 銭江浩, 田中耕三, 安井明

第41回染色体ワークショップ　2024/01
Transcription–replication conflictsにおけるクロマチン構造変化とDNA修復経路

宇井彩子

第46回日本分子生物学会　2023/11
A BET-family protein BRD3 is involved in Homologous recombination and affects PARP inhibitor resistance

Qian Jianghao, Reiko Watanabe, Tomoko Watanabe, Kozo Tanaka, Takashi Kohno, Akira Yasui, Ayako Ui

2023/09
Chromatin remodeler, ISWI, alters chromatin structure to promote Homologous Recombination, mobilizing DNA polymerase at DSBs

2023/06/05
ヒストンメチル化酵素MLLのDSB修復における新規機能 Invited

宇井彩子

日本分子生物学会　2019/12/06
DSBシグナル伝達と修復におけるPRC1とヒストンユビキチン化に関する分子機能解析 Invited

宇井彩子

日本分子生物学会　2018/12/29
DSBシグナル伝達と修復におけるPRC1とヒストンユビキチン化に関する分子機能解析 Invited

宇井彩子

2018/12/03
DSBシグナル伝達と修復におけるヒストン修飾因子とクロマチンリモデリング複合体の機能解析 Invited

宇井彩子

日本放射線影響学会　2018/11/07
DSBシグナル伝達と修復におけるヒストン修飾因子とクロマチンリモデリング複合体の機能解析 Invited

宇井彩子

日本放射線影響学会　2018/10
DSB修復におけるヒストンメチル化H3K4の機能 Invited

宇井彩子

日本遺伝学会　2018/09/21
DSB 修復を制御するUbiquitin E3-ligase の新規機能

宇井彩子

第３５回染色体ワークショップ　2017/12/21
DSB修復に関わる新規Ubiquitin E3-ligaseの機能解析 Invited

宇井彩子

日本分子生物学会　2017/12/09
DSB修復に関わる新規Ubiquitin E3-ligaseの機能解析 Invited

宇井彩子

日本分子生物学会　2017/12/06
DSB修復に関わる新規Ubiquitin E3-ligaseの新規制御機構の解明

宇井彩子

第24回DNA複製・組換え・修復ワークショップ　2017/11/28
The role of DSB repair and checkpoint during transcription for genome stability International-presentation Invited

Ayako Ui

The 2nd Biosignal Research Center International Symposium, Environmental Stress and Genome Damage Response: Biosignals from Molecule to Disease　2017/11/21
The role of DSB repair and checkpoint during transcription for genome instability. Invited

宇井彩子

ICEM satellite symposium　2017/11/20
DSB修復を制御するUbiquitin E3-ligaseの新規機能 Invited

宇井彩子

日本放射線影響学会　2017/10/25
DSB修復を制御するUbiquitin E3-ligaseの新規機能 Invited

宇井彩子

日本放射線影響学会　2017/10/13
DSB修復に関与する新規Ubiquitin E3-ligaseの機能解析 Invited

宇井彩子

国立遺伝学研究所「染色体構築と安定化を担う分子機構」　2017/10/02
プロテアソーム結合因子のUBE3Cはプロテアソーム阻害剤によるがん細胞死を増強する

宇井彩子

日本癌学会　2017/09/28
DSB修復を制御するUbiquitin E3-ligaseの新規機能 Invited

宇井彩子

日本遺伝学会　2017/09/13
DSB修復を制御するUbiquitin E3-ligaseの新規機能

宇井彩子

日本遺伝学会　2017/09/05
Recent progress in DNA damage repair research:Crosstalk between DSB signaling/repair and Protein Homeostasis in genome instability Invited

DNA障害応答に関する研究指導および分子生物学セミナー　2017/06/07
新規Ubiquitin E3-ligaseのDSB修復を介した染色体安定性機構

宇井彩子

核内動態研究会　2017/02/03
ゲノム不安定性におけるDSB損傷シグナル/修復機構と蛋白質恒常性維持機構の共役 Invited

2017/01/19
新規Ubiquitin E3-ligaseのDSB修復を介した染色体安定機構

宇井彩子

染色体ワークショップ・核ダイナミクス研究会　2017/01/11
DSB修復と転写の共役機構とゲノムの安定性 Invited

日本大学セミナー　2016/12/14
DSB修復に関与する新規Ubiquitin E3-ligaseの機能解析 Invited

宇井彩子

日本分子生物学会　2016/12/02
Chromatin remodeling complexes belonging to ISWI and SWI/SNF families cooperatively promote DSB repair to prevent genome instability. International-presentation

3R symposium　2016/11/15
DSB修復に関与する新規Ubiquitin E3-ligaseの機能解析 Invited

宇井彩子

国立遺伝研研究会　2016/10/24
DNA損傷修復と転写の共役機構と染色体安定性 Invited

宇井彩子

第9回Symphony　2016/09/19

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Research Projects 7

Analysis of RNA Processing Abnormalities as Determinants of Responsiveness to Cancer Immunotherapy

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: National Cancer Center Japan

2025/04/01 - 2028/03/31
Mechanism for Multiplex Nicks-induced interhomolog homologous recombination

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Osaka University

2022/04/01 - 2026/03/31
Muliple nicks-induced interhomolog recombination

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Osaka University

2022/04/01 - 2026/03/31
DNA2本鎖切断修復制御の中核となるユビキチン依存的DNA損傷応答の解明

中田慎一郎, 宇井彩子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(B)

Institution: 大阪大学

2019/04/01 - 2022/03/31

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DNA2本鎖損傷（DSB）応答（DDR）において、ユビキチン化はリン酸化と並び中心的な翻訳後修飾である。ここ約10年間に様々な研究成果が発表されてきたにもかかわらず、RNF8-RNF168依存的なDDRには、いくつかの根本的な謎が未解明のまま残されている。本研究ではRNF8-RNF168経路における未解明事項の解明を目的としている。この目的を達成するために、クロマチンテザリングの実験系を用いることで、RNF8の真のターゲットを同定し、これを手がかりに研究を展開するべく実験を進めた。特定のクロマチンにRNF8をテザリングさせるために、TetRと蛍光物質Cherryのついたプラスミドを作成した。このプラスミドを、TREサイトを約200コピーゲノムに持つ細胞にトランスフェクションし、クロマチン部位に結合するタンパク質、あるいはヒストン修飾因子などを免疫染色で検出した。その結果、RNF8経路のシグナルに関わる既知因子がクロマチンに結合することが観察できた。生理的なDDRを研究するため、RNF8恒常発現細胞の樹立を試みた。しかし、繰り返し樹立を試みたものの、実施したすべての実験において、恒常発現細胞の樹立に至らなかった。一過性にRNF8が過剰発現の状態となることが細胞毒性を誘導することが原因であると考えている。このため、当初予定していたように研究を遂行することが困難となった。そこで、当初、上記の手法により候補遺伝子を選択してから実施する予定であった遺伝子ノックダウン実験を、文献やデータベースより候補遺伝子を抽出して実施する方法へと変更した。10弱の候補遺伝子を絞り込んだ後、それらに対する特異的なsiRNAを複数作成し、遺伝子の一過性ノックアウトによる相同組み換えおよび非相同末端結合への影響を測定した。その結果、複数の遺伝子において、DNA修復効率の顕著な低下が認められた。
Investigation of the mechanism underlying the association between DSB repair and Transcription

UI Ayako

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tokyo University of Technology

2017/06/30 - 2019/03/31

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DSB (DNA double strand break) is one of harmful DNA damage that induces cancer. Recently, DSB-induces transcriptional repression prevents genome instability and cancer. In this study, we investigated the relationship between DSB-induced transcriptional repression, DSB repair and transcription. We found that factors of histone ubiquitination which have been reported to be involved in transcription and DSB repair are required for DSB-induced transcriptional repression. In addition, we identify the histone modifications that are required for DSB-induced transcriptional repression. These findings may be an important information to reveal the mechanism of genome instability and cancer.
Function of MLL fusion partner ENL in DSB repair

UI Ayako

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

2014/04/01 - 2017/03/31

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ENL (MLLT1), a factor of Super Elongation Complex (SEC) and fusion partner of the Mixed-Lineage-Leukemia (MLL) protein, activates transcription. Here we found that ENL interacts with BMI1/RING1B, the E3-ubiquitin-ligase of PRC1 (Polycomb Repressive Complex 1). After DSB, ENL is phosphorylated by ATM at its well-conserved SQ-sites and increase its interaction with BMI1. Then, ENL recruits Polycomb at transcription sites near DSBs to repress transcription by promoting ubiquitination of H2A. Furthermore, the function of ENL is required for the recruitment of DSB repair proteins at DSB sites near transcription sites and DSB repair. These results suggest that under the control of ATM, ENL recruits PRC1 at transcriptional elongation sites to repress transcription and promotes DSB repair. This mechanism ensures a rapid and systematic transcriptional repression by DSBs to secure cellular homeostasis and genome integrity.
LKB1-AMPK2 signaling promotes non-homologous end joining by regulating SWI/SNF chromatin remodeling

UI Ayako

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

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

Institution: Tohoku University

2012/04/01 - 2014/03/31

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LKB1 regulates multiple processes by phosphorylating adenosine monophosphate–activated protein kinases (AMPKs). LKB1 and AMPK2 proteins were found here to be recruited to DNA double strand break (DSB) sites. Their depletion or inhibition compromises the ability of cells to repair DNA by non-homologous end joining (NHEJ) by suppressing accumulation of KU70, a key NHEJ protein, and of BRM, a catalytic subunit in the SWI/SNF complex to DSB sites, resulting in the occurrence of chromosome breaks. Histone H2B mutants lacking AMPK2 phoshorylation site impaired the KU70 and BRM recruitment. LKB1-AMPK2 signaling is likely to regulate NHEJ and contribute to genome stability.

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