Analysis of a new genetic disorder caused by the deficiency in radiation-induced DNA double-strand break repair
Project/Area Number |
15H05333
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Risk sciences of radiation and chemicals
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Research Institution | Nagasaki University |
Principal Investigator |
NAKAZAWA Yuka 長崎大学, 原爆後障害医療研究所, 助教 (00533902)
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Research Collaborator |
JEGGO Penny
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2015: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
|
Keywords | 修復 / DNA修復 / NHEJ / 遺伝性疾患 |
Outline of Final Research Achievements |
We analyzed an uncharacterised Cockayne syndrome like patient with normal NER (nucleotide excision repair) activity. We performed next-generation exome sequencing and identified pathogenic mutations in the XRCC4 gene, which encodes a non-homologous end joining (NHEJ) protein required for the ligation process. Our XRCC4 syndrome patient retained normal immune response, although LIG4 syndrome patients usually display immunodeficiency. Fibroblast cell lines derived from the XRCC4 and LIG4 patients showed significant radiation sensitivity. We performed plasmid-based V(D)J recombination assays for the XRCC4 patient cell lines. We are currently establishing model mice to further study molecular pathogeneses of XRCC4 syndrome.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.2018
Author(s)
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.
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Journal Title
Journal of Human Genetics
Volume: 63
Pages: 417-423
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome.2018
Author(s)
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 A.
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Journal Title
Journal of Medical Genetics
Volume: 55
Pages: 329-343
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites.2018
Author(s)
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.
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Journal Title
PLoS Genetics
Volume: 14
Pages: e1007277
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair.2017
Author(s)
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.
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Journal Title
PLos One
Volume: 12
Pages: e0188320
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells.2017
Author(s)
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.
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Journal Title
Scientific Reports
Volume: 7
Pages: 8447
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A ten-year follow up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole genome sequencing.2016
Author(s)
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
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Journal Title
Photodermatol Photoimmunol Photomed
Volume: 32
Pages: 174-180
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly- progressing radiosensitive-severe combined immunodeficiency.2015
Author(s)
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.
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Journal Title
Journal of Clinical Immunology
Volume: 160
Pages: 255-260
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency.2015
Author(s)
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.
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Journal Title
Journal of Allergy and Clinical Immunology
Volume: 136
Pages: 1007-1017
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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