Laboratories

Molecular Genetics

KEYWORDS

  • DNA repair
  • transcription-coupled repair

HEAD

NAKAZAWA Yuka

Professor

Researchers

LAB MEMBER

Faculty Position Researchers
ITO, Mikako Lecturer Researchers
HAMAGUCHI Tomonari Designated Lecturer (Medical Innovation Unit) Researchers
TSUKADA Kotaro Designated Assistant Professor Researchers

CONTACT

Email molgenetngo◎gmail.com (Please send a message after replacing "◎" mark with "@" mark. )
HP Private Page

OUTLINE

In our laboratory, we pursue new research fields focusing on “DNA repair mechanisms” and “diseases caused by the accumulation of DNA damage”, based on disease-oriented genomic analyses and the application of next-generation sequencing technologies. Through these studies, we aim to establish a strong foundation in basic medical research and to develop a technological platform that bridges basic and clinical applications.

We believe that the mission of basic medical researchers is to address fundamental questions in life science, to contribute to society through a comprehensive understanding of diseases and the development of novel therapeutic strategies, and to train young researchers who will carry this mission forward. Our laboratory welcomes young scientists and physicians aspiring to become researchers. We provide a research environment that fosters open and active discussion, collaboration, and the maximization of each individual’s potential.

We look forward to pursuing new discoveries together with highly motivated young physicians and researchers.

RESEARCH PROJECTS

It is essential to understand overall biological systems in order to elucidate the mechanisms underlying the onset of various human diseases. Among these, elucidation of the fundamental mechanisms underlying the maintenance, transmission, and regulation of genetic information represents one of the most important challenges. The DNA damage response and DNA repair (DDR) is essential for maintaining genome stability, and defects in DDR are associated with various pathological conditions, including cancer and premature aging. In particular, dysfunction of the transcription-coupled repair (TCR) system, which is responsible for maintaining genomic stability by rapidly removing DNA damage that arises in transcribed regions of genes, is closely associated with the onset of genetic diseases such as cancer predisposition and premature aging. We are conducting research focused on the transcription-coupled repair (TCR) mechanism to better understand the molecular basis of various diseases and to develop novel diagnostic and therapeutic strategies.

Furthermore, in our laboratory, we integratively promote basic research and clinical applications based on insights gained into DDR functions that maintain genome stability, with the long-term goal of developing technologies that will contribute to the diagnosis and treatment of a wide range of diseases. Diseases caused by defects in DNA repair mechanisms are rare disorders that are often difficult to diagnose and treat. Therefore, we aim to contribute to the establishment of diagnostic and therapeutic strategies for these diseases through collaboration with international research networks. In our laboratory, we possess advanced analytical platforms based on state-of-the-art next-generation sequencing (NGS) technologies, which can be applied to the detection of DNA damage in vivo and to the identification of disease-causing mechanisms. By using multi-omics analyses, we seek to achieve a comprehensive understanding of disease-specific characteristics, elucidate the molecular mechanisms underlying disease onset, and ultimately facilitate the realisation of personalised medicine. Through bridging basic research and clinical studies, our goal is to establish novel therapeutic strategies for intractable diseases.

  1. Molecular mechanisms of DNA repair
  2. Identification of disease-causing genetic variants
  3. Elucidation of the molecular pathogenesis of hereditary diseases
  4. Drug discovery for intractable hereditary diseases
  5. Development of mouse models for neurodegenerative diseases

BIBLIOGRAPHY

2025
  1. Nakazawa Y*, Ye L*, Oka Y*, Morinaga H, Kato K, Shimada M, Tsukada K, Tsujikawa K, Nishio Y, Fassihi H, Mohammed S, Lehmann AR, Ogi T. TFIIH-p52∆C defines a ninth xeroderma pigmentosum complementation-group XP-J and restores TFIIH stability to p8-defective trichothiodystrophy. Journal of Clinical Investigation : e195732. Online ahead of print.　(2025). doi: 10.1172/JCI195732.
  2. Fassihi H*, Mohammed S, Nakazawa Y*, Fawcett H*, Turner S, Palfrey J, Garrood I, Abiona A, Morley AM, Shimada M, Kato K, Lehmann AR, Ogi T. XP-J, a ninth xeroderma pigmentosum complementation group, results from mutations in GTF2H4, encoding TFIIH-p52 subunit. Journal of Clinical Investigation:e195731. Online ahead of print. (2025). doi: 10.1172/JCI195731.
  3. Ebata A, Takeichi T, Nishida K, Chretien B, Miyazaki A, Yoshikawa T, Suzuki Y, Tanahashi K, Fukaura R, Seishima M, Suga Y, Muro Y, Nakazawa Y, Ogi T, Akiyama M. Estimating the proportions of allele frequencies for SERPINA12 pathogenic variants in Japanese patients with Nagashima-type palmoplantar keratosis/keratoderma. British Journal of Dermatology 193(1):184-185. (2025). doi: 10.1093/bjd/ljaf111.
  4. Nakazawa Y, Oka Y, Matsunaga T, Ogi T. Transcription-coupled repair - mechanisms of action, regulation, and associated human disorders. FEBS Letters 599(2): 166-167 (2025). doi: 10.1002/1873-3468.15073.
  5. Omi M, Takeichi, Yoshikawa T, Inoue Y, Fukaura R, Hattori I, Nakazawa Y, Noda T, Muro Y, Akiyama M. Comparing the severity of epidermolysis bullosa simplex harboring KRT5 variants with the AlphaMissense score.Journal of Dermatology 52(3): e235-e237 (2025). doi: 10.1111/1346-8138.17488.
2024
  1. Oka Y, Nakazawa Y, Shimada M, Ogi T. Endogenous aldehyde-induced DNA-protein crosslinks are resolved by transcription-coupled repair. Nature Cell Biology 26(5): 784-796 (2024). doi: 10.1038/s41556-024-01401-2.
2023
  1. Tomita A, Sasanuma H, Owa T, Nakazawa Y, Shimada M, Fukuoka T, Ogi T, Nakada S. Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells. Nature Communications 14(1): 5607 (2023). doi: 10.1038/s41467-023-41048-5.
  2. Senju C*, Nakazawa Y*, Oso T*, Shimada M, Kato K, Matsuse M, Tsujimoto M, Masaki T, Miyazaki Y, Fukushima S, Tateishi S, Utani A, Murota H, Tanaka K, Mitsutake N, Moriwaki S, Nishigori C, Ogi T. Deep intronic founder mutations identified in the ERCC4/XPF gene are potential therapeutic targets for a high-frequency form of xeroderma pigmentosum. PNAS 120(27): e2217423120 (2023). doi: 10.1073/pnas.2217423120.
  3. Tsujimoto M, Nakano E,Nakazawa Y, Kanda F, Ueda T, Ogi T, Nishigori C. A case of Cockayne syndrome with unusually mild clinical manifestations. Journal of Dermatology 50 (4): 541-545 (2023). doi: 10.1111/1346-8138.16679.
2022
  1. Senju C, Nakazawa Y, Shimada M, Iwata D, Matsuse M, Tanaka K, Miyazaki Y, Moriwaki S, Mitsutake N, Ogi T. Aicardi-Goutières syndrome with SAMHD1 deficiency can be diagnosed by unscheduled DNA synthesis test.Frontiers in Pediatrics 10: 1048002 (2022). doi: 10.3389/fped.2022.1048002.
2021
  1. Jia N, Guo C*,Nakazawa Y*, van den Heuvel D*, Luijsterburg MS, Ogi T. Dealing with transcription-blocking DNA damage: Repair mechanisms, RNA polymerase II processing and human disorders. DNA Repair 106: 103192 (2021). doi: 10.1016/j.dnarep.2021.103192.
  2. van der Weegen Y, de Lint K, van den Heuvel D, Nakazawa Y, Mevissen TET, van Schie JJM, San Martin Alonso M, Boer DEC, González-Prieto R, Narayanan IV, Klaassen NHM, Wondergem AP, Roohollahi K, Dorsman JC, Hara Y, Vertegaal ACO, de Lange J, Walter JC, Noordermeer SM, Ljungman M, Ogi T, Wolthuis RMF, Luijsterburg MS. ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation. Nature Cell Biology 23(6): 595-607 (2021). doi: 10.1038/s41556-021-00688-9.
2020
  1. Oka Y, Hamada M*, Nakazawa Y*, Muramatsu H*, Okuno Y*, Higasa K*, Shimada M, Takeshima H, Hanada K, Hirano T, Kawakita T, Sakaguchi H, Ichimura T, Ozono S, Yuge K, Watanabe Y, Kotani Y, Yamane M, Kasugai Y, Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, Mizuno S, Miyake N, Kawai Y, Tokunaga K, Nagasaki M, Kito S, Isoyama K, Onodera M, Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T. Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome. Science Advances 6(51): eabd7197 (2020). doi: 10.1126/sciadv.abd7197.
  2. Saha LK, Wakasugi M, Akter S, Prasad R, Wilson SH, Shimizu N, Sasanuma H, Huang SN, Agama K, Pommier Y, Matsunaga T, Hirota K, Iwai S, Nakazawa Y, Ogi T, Takeda S. Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells. PNAS 117(25): 14412-14420 (2020). doi: 10.1073/pnas.1920165117.
  3. Kato K, Oka Y, Muramatsu H, Vasilev FF, Otomo T, Oishi H, Kawano Y, Kidokoro H, Nakazawa Y, Ogi T, Takahashi Y, Saitoh S. Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. Journal of Medical genetics 57(4): 245-253 (2020). doi: 10.1136/jmedgenet-2019-106213.
  4. Nakazawa Y, Hara Y, Oka Y, Komine O, Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Katoh K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg M, Ogi T. Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair. Cell 180(6): 1228-1244 (2020). doi: 10.1016/j.cell.2020.02.010.
2019
  1. Kono M, Kodera M, Inasaka Y, Hasegawa I, Muro Y, Nakazawa Y, Ogi T, Akiyama M. Hailey-Hailey disease with oesophageal involvement due to a previously unreported ATP2C1 mutation.European Journal of Dermatology 2019 Online ahead of print.
  2. Shiraiwa K, Matsuse M, Nakazawa Y, Ogi T, Suzuki K, Saenko V, Xu S, Umezawa K, Yamashita S, Tsukamoto K, Mitsutake N. JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells. Thyroid 29(5): 674-682 (2019). doi: 10.1089/thy.2018.0212.
  3. Kono M, Sawada M, Nakazawa Y, Ogi T, Muro Y, Akiyama M. A Japanese Case of Galli-Galli Disease due to a Previously Unreported POGLUT1 Mutation. Acta Dermato Venereologica 99(4): 458-459 (2019). doi: 10.2340/00015555-3119.
2018
  1. Calmels N, Botta E, Jia N, Fawcett H, Nardo T, Nakazawa Y, Lanzafame M, Moriwaki S, Sugita K, Kubota M, Obringer C, Spitz MA, Stefanini M, Laugel V, Orioli D, Ogi T, Lehmann AR. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome. Journal of Medical Genetics 55(5): 329-343 (2018). doi: 10.1136/jmedgenet-2017-104877.
  2. Doi H, Koyano S, Miyatake S, Nakajima S, Nakazawa Y, Kunii M, Tomita-Katsumoto A, Oda K, Yamaguchi Y, Fukai R, Ikeda S, Kato R, Ogata K, Kubota S, Hayashi N, Takahashi K, Tada M, Tanaka K, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ogi T, Aihara M, Takeuchi H, Matsumoto N, Tanaka F. Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations. Journal of Human Genetics63(4): 417-423 (2018). doi: 10.1038/s10038-017-0408-5.
  3. Yasuda T, Kagawa W, Ogi T, Kato TA, Suzuki T, Dohmae N, Takizawa K, Nakazawa Y, Genet MD, Saotome M, Hama M, Konishi T, Nakajima NI, Hazawa M, Tomita M, Koike M, Noshiro K, Tomiyama K, Obara C, Gotoh T, Ui A, Fujimori A, Nakayama F, Hanaoka F, Sugasawa K, Okayasu R, Jeggo PA, Tajima K. Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. PLoS Genetics 14(3): e1007277 (2018). doi: 10.1371/journal.pgen.1007277.
2017
  1. Tsuda M, Cho K, Ooka M, Shimizu N, Watanabe R, Yasui A, Nakazawa Y, Ogi T, Harada H, Agama K, Nakamura J, Asada R, Fujiike H, Sakuma T, Yamamoto T, Murai J, Hiraoka M, Koike K, Pommier Y, Takeda S, Hirota K. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair. PLos One 12(11): e0188320 (2017). doi:10.1371/journal.pone.0188320.
  2. Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways. Nucleic Acids Research 45(22):13043-13055 (2017). doi: 10.1093/nar/gkx970.
  3. Doi R, Tsuchiya T, Mitsutake N, Nishimura S, Matsuu-Matsuyama M, Nakazawa Y, Ogi T, Akita S, Yukawa H, Baba Y, Yamasaki N, Matsumoto K, Miyazaki T, Kamohara R, Hatachi G, Sengyoku H, Watanabe H, Obata T, Niklason LE, Nagayasu T. Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells.Scientific Reports 7(1): 8447 (2017). doi: 10.1038/s41598-017-09115-2.
  4. 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. Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair. Nature Communications 8: 16102 (2017). doi: 10.1038/ncomms16102.
  5. Y, Etheridge TJ, Nakazawa Y, Nakayama M, Watson AT, Miyabe I, Ogi T, Osborne MA, Carr AM. PCNA ubiquitylation ensures timely completion of unperturbed DNA replication in fission yeast. PLoS Genetics13(5): e1006789 (2017). doi: 10.1371/journal.pgen.
  6. Takahashi Y, Endo Y, Kusaka-Kikushima A, Nakamaura S, Nakazawa Y, Ogi T, Uryu M, Tsuji M, Furue M, Moriwaki S. An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities. British Journal of Dermatology177(1): 253-257 (2017). doi: 10.1111/bjd.15051.
2016
  1. Ono R, Masaki T, Mayca Pozo F, Nakazawa Y, Swagemakers SM, Nakano E, Sakai W, Takeuchi S, Kanda F, Ogi T, van der Spek PJ, Sugasawa K, Nishigori C. A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing. Photodermatology Photoimmunology & Photomedicine 32(4): 174-180 (2016). doi: 10.1111/phpp.12240.
2015
  1. Guo C*, Nakazawa Y*, Woodbine L*, Bjorkman A, Shimada M, Fawcett H, Jia N, Ohyama K, Li TS, Nagayama Y, Mitsutake N, Pan-Hammarstrom Q, Gennery AR, Lehmann AR, Jeggo PA, Ogi T. XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency. Journal of Allergy and Clinical Immunology 136(4): 1007-1017 (2015). doi: 10.1016/j.jaci.2015.06.007.
  2. Tamura S, Higuchi K, Tamaki M, Inoue C, Awazawa R, Mitsuki N, Nakazawa Y, Mishima H, Takahashi K, Kondo O, Imai K, Morio T, Ohara O, Ogi T, Furukawa F, Inoue M, Yoshiura K, Kanazawa N. Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly- progressing radiosensitive-severe combined immunodeficiency. Journal of Clinical Immunology 160(2): 255-260 (2015)doi: 10.1016/j.clim.2015.07.004.
2014
  1. Jia N*, Nakazawa Y*, Guo C, Shimada M, Sethi M, Takahashi Y, Ueda H, Nagayama Y, T. A rapid, comprehensive system for assaying DNA repair activity and cytotoxic effects of DNA-damaging reagents. Nature Protocols 10(1): 12-24 (2015). doi: 10.1038/nprot.2014.194.
  2. Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH. Hypomorphic PCNA mutation underlies a human DNA repair disorder. Journal of Clinical Investigation 124(7): 3137-3146 (2014). doi: 10.1172/JCI74593.
2013
  1. Kashiyama K*, Nakazawa Y*, Pilz D*, Guo C*, Shimada M, Sasaki K, Fawcett H, Wing J, Lewin S, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Yamashita S, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Takahashi Y, Nagayama Y, Mitsutake N, Lehmann AR, Ogi T. Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia. American Journal of Human Genetics 92(5): 807-819 (2013). doi: 10.1016/j.ajhg.2013.04.007.
2012
  1. Ogi T, Walker S, Stiff T, Hobson, E, Limsirichaikul S, Carpenter G, Prescott K, Suri M, Byrd PJ, Matsuse M, Mitsutake N, Nakazawa Y, Vasudevan P, Barrow M, Stewart GS, Taylor AMR, O'Driscoll M, Jeggo PA. Identification of the First ATRIP-Deficient Patient and Novel Mutations in ATR Define a Clinical Spectrum for ATR-ATRIP Seckel Syndrome. PLoS Genetics 8(11): e1002945 (2012). doi: 10.1371/journal.pgen.1002945.
  2. Nakazawa Y*, Sasaki K*, Mitsutake N*, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura KI, Ogi T. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Nature Genetics 44(5): 586-592 (2012). doi: 10.1038/ng.2229.
2011
  1. Matsumoto Y, Miyamoto T, Sakamoto H, Izumi H, Nakazawa Y, Ogi T, Tahara H, Oku S, Hiramoto A, Shiiki T, Fujisawa Y, Ohashi H, Sakemi Y, Matsuura S. Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly. DNA Repair 10(3): 314-321 (2011). doi: 10.1016/j.dnarep.2010.12.002.
2010
  1. Ogi T, Limsirichaikul S*, Overmeer R*, Volker M*, Takenaka K*, Cloney R*, Nakazawa Y*, Niimi A, Miki Y, Jaspers N, Mullenders L, Yamashita S, Fousteri M, Lehmann AR. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Molecular Cell 37(5): 714-727 (2010). doi: 10.1016/j.molcel.2010.02.009.
  2. Nakazawa Y, Yamashita S, Lehmann AR, Ogi T. A semi-automated non-radioactive system for measuring recovery of RNA synthesis and unscheduled DNA synthesis using ethynyluracil derivatives. DNA Repair 9(5): 506-516 (2010). doi: 10.1016/j.dnarep.2010.01.015.
  3. Takatsuji T, Takayanagi H, Morishita K, Nojima K, Furusawa Y, Nakazawa Y, Matsuse M, Akamatsu S, Hirano N, Hirashima N, Hotokezaka S, Ijichi T, Kakimoto C, Kanemaru T, Koshitake M, Moriuchi A, Yamamoto K, Yoshikawa I. Induction of micronuclei in germinating onion seed root tip cells irradiated with high energy heavy ions. Journal of radiation research (Tokyo) 51(3): 315-323 (2010). doi :10.1269/jrr.09028
2009
  1. Matsuse M, Mitsutake N, Rogounovitch T, Saenko V, Nakazawa Y, Rumyantsev P, Lushnikov E, Suzuki K, Yamashita S. Mutation analysis of RAP1 gene in papillary thyroid carcinomas. Endocrine Journal 56(1): 161-164 (2009). doi: 10.1507/endocrj.k08e-244.
2008
  1. Nakazawa Y, Saenko V, Rogounovitch T, Suzuki K, Mitsutake N, Matsuse M, Yamashita S. Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage. International Journal of Radiation Oncology Biology Physics 71(2): 567-577 (2008). doi: 10.1016/j.ijrobp.2007.10.036.
  2. Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko V, Rogounovitch T, Nakazawa Y, Hayashi T, Ohtsuru A, Yamashita S. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Science 99(6): 1147-1154 (2008).
  3. Matsuse M, Saenko V, Sedliarou I, Rogounovitch T, Nakazawa Y, Mitsutake N, Akulevich N, Namba H, Yamashita S. A novel role for thyroid hormone receptor beta in cellular radiosensitivity. Journal of Radiation Research (Tokyo) 49(1): 17-27 (2008). doi: 10.1269/jrr.07065.
2007
  1. Sedliarou I, Matsuse M, Saenko V, Rogounovitch T, Nakazawa Y, Mitsutake N, Namba H, Nagayama Y, Yamashita S. Overexpression of wild-type THRbeta1 suppresses the growth and invasiveness of human papillary thyroid cancer cells. Anticancer Research 27(6B): 3999-4009 (2007).

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